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Sample records for striatal da levels

  1. A Comparative study for striatal-direct and -indirect pathway neurons to DA depletion-induced lesion in a PD rat model.

    Science.gov (United States)

    Zheng, Xuefeng; Wu, Jiajia; Zhu, Yaofeng; Chen, Si; Chen, Zhi; Chen, Tao; Huang, Ziyun; Wei, Jiayou; Li, Yanmei; Lei, Wanlong

    2018-04-16

    Striatal-direct and -indirect Pathway Neurons showed different vulnerability in basal ganglia disorders. Therefore, present study aimed to examine and compare characteristic changes of densities, protein and mRNA levels of soma, dendrites, and spines between striatal-direct and -indirect pathway neurons after DA depletion by using immunohistochemistry, Western blotting, real-time PCR and immunoelectron microscopy techniques. Experimental results showed that: 1) 6OHDA-induced DA depletion decreased the soma density of striatal-direct pathway neurons (SP+), but no significant changes for striatal-indirect pathway neurons (ENK+). 2) DA depletion resulted in a decline of dendrite density for both striatal-direct (D1+) and -indirect (D2+) pathway neurons, and D2+ dendritic density declined more obviously. At the ultrastructure level, the densities of D1+ and D2+ dendritic spines reduced in the 6OHDA groups compared with their control groups, but the density of D2+ dendritic spines reduced more significant than that of D1. 3) Striatal DA depletion down-regulated protein and mRNA expression levels of SP and D1, on the contrary, ENK and D2 protein and mRNA levels of indirect pathway neurons were up-regulated significantly. Present results suggested that indirect pathway neurons be more sensitive to 6OHDA-induced DA depletion. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

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    McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

    1990-01-01

    Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

  3. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

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    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-07-01

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

  4. Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

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    Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

    2014-09-01

    Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  5. Striatal volume predicts level of video game skill acquisition.

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    Erickson, Kirk I; Boot, Walter R; Basak, Chandramallika; Neider, Mark B; Prakash, Ruchika S; Voss, Michelle W; Graybiel, Ann M; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

    2010-11-01

    Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.

  6. Brain Pharmacokinetics and the Pharmacological Effects on Striatal Neurotransmitter Levels of Pueraria lobata Isoflavonoids in Rat

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    Bingxin Xiao

    2017-09-01

    Full Text Available Isoflavonoids are putatively active components of Pueraria lobata and has been demonstrated prominent neuro-protection effect against cerebrovascular disorders, hypertension or Parkinson's disease (PD. However, the molecular basis for the beneficial effect of Pueraria lobata on nervous systems has not been well revealed. The present study aims to assess striatum exposure to main active isoflavonoids and changes of striatal extracellular neurotransmitters levels in rat brain after intravenous administration of Pueraria lobata isoflavonoids extracts (PLF, to further elucidate its' substantial bases for neuro activities. Fifteen rats were divided into 3 groups (five rats in each group to receive a dose of PLF at 80 or 160 mg/kg or normal saline (vehicle, respectively. An LC-MS/MS method was employed to determine the concentrations of five main isoflavonoids and multiple neurotransmitters in microdialysate from striatal extracellular fluid (ECF of the rats. The exposed quantities of puerarin (PU, 3′-methoxypuerarin (MPU, daidzein-8-C-apiosyl-(1-6-glucoside (DAC, and 3′-hydroxypuerarin (HPU in striatum were dose-dependent. The content of daidzein (DAZ was too low to be detected in all dialysate samples through the experiment. Optimal dose PLF (80 mg/kg promoted DA metabolism and inhibited 5-HT metabolism. No obvious change in the level of GLu was determined. The concentration of GABA presented a temporary decline firstly and then a gradual uptrend followed by a further downtrend. Higher dose (160 mg/kg PLF could enhance the metabolism of both DA and 5-HT, and lower the extracellular level of GLu, without changing GABA concentrations, which might result in alleviation on excitatory toxicity under conditions, such as ischemia. The results infer that different dose of PLF should be chosen to achieve appropriate neurochemical modulation effects under conditions, such as hypertension or ischemia/stroke. These findings may significantly contribute to a

  7. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration

    DEFF Research Database (Denmark)

    Ziebell, Morten; Khalid, Usman; Klein, Anders B

    2012-01-01

    Compelling evidence has shown, that neurotrophins responsible for the regulation of neuronal growth, survival, and differentiation are involved in neurodegenerative diseases. Whereas lower serum levels of brain derived neurotrophic factor (BDNF) have been observed in patients with Parkinson...

  8. Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

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    Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

    2014-05-01

    Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by

  9. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

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    Ismael Huertas

    Full Text Available Parkinson's disease (PD patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA, a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36, intermediate (I, n = 22, and tremor-dominant (TD, n = 17 subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001 and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25% and I (45% patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  10. Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

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    Lavoute, Cécile; Weiss, Michel; Risso, Jean-Jacques; Rostain, Jean-Claude

    2014-02-01

    The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

  11. MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

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    Weihmuller, F B; O'Dell, S J; Marshall, J F

    1992-06-01

    Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

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    Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

    2014-02-01

    Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

  13. Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

    International Nuclear Information System (INIS)

    Wolf, M.E.

    1986-01-01

    Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K + , however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with [ 3 H]-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K + -evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis

  14. Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.

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    Daniele, Thiago Medeiros da Costa; de Bruin, Pedro Felipe Carvalhedo; Rios, Emiliano Ricardo Vasconcelos; de Bruin, Veralice Meireles Sales

    2017-08-14

    Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Parsing Heterogeneous Striatal Activity

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    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  16. Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers

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    Yansong eLi

    2014-03-01

    Full Text Available Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs, we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.

  17. Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers.

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    Li, Yansong; Sescousse, Guillaume; Dreher, Jean-Claude

    2014-01-01

    Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs), we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI) and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.

  18. Níveis dos neurotransmissores estriatais durante o estado epiléptico Striatal monoamines levels during status epilepticus

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    Rivelilson Mendes de Freitas

    2003-01-01

    Full Text Available O objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.; P400 e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido diidroxifenilacético e aumento na concentração do ácido 5-hidroxiindolacético. Nenhuma alteração foi observada no 4-hidroxi-3-metoxi-fenilacético. Os resultados sugerem que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo no corpo estriado de ratos desenvolvidos.The purpose of the present work to investigate the striatal neurotransmissors level in adult rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400 mg/kg; s.c.; P400 and the controls received saline. Adult animals were closed observed for behavioural changes during 1h. In this period, the animals that developed status epilepticus and survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determiden by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid was reduced and an concentration increase in 5-hydroxyindolacetic acid. Didn't observed alteration in 4-hydroxy-3-methoxy-phenylacetic acid. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in rat mature striatum.

  19. Individual differences in the motivation to communicate relate to levels of midbrain and striatal catecholamine markers in male European starlings

    OpenAIRE

    Heimovics, Sarah A; Salvante, Katrina G; Sockman, Keith W; Riters, Lauren V

    2011-01-01

    Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal ...

  20. No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [I-123]FP-CIT (DaTSCAN) and SPECT

    NARCIS (Netherlands)

    Thomsen, Gerda; Knudsen, Gitte Moos; Jensen, Peter S.; Ziebell, Morten; Holst, Klaus K.; Asenbaum, Susanne; Booij, Jan; Darcourt, Jacques; Dickson, John C.; Kapucu, Ozlem L.; Nobili, Flavio; Sabri, Osama; Sera, Terez; Tatsch, Klaus; Tossici-Bolt, Livia; van Laere, Koen; Borght, Thierry Vander; Varrone, Andrea; Pagani, Marco; Pinborg, Lars Hageman

    2013-01-01

    Background: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D-2-like

  1. DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

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    Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

    2013-01-01

    The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

  2. Running wheel exercise before a binge regimen of methamphetamine does not protect against striatal dopaminergic damage.

    Science.gov (United States)

    O'dell, Steven J; Marshall, John F

    2014-09-01

    Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic nerve terminals as measured by decreases in tissue dopamine (DA) content and levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell bodies from which the DA terminals arise survive, and previous reports show that striatal DA markers return to control levels by 12 months post-mAMPH, suggesting long-term repair or regrowth of damaged DA terminals. We previously showed that when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced decreases in striatal DAT. However, these data left unresolved the question of whether exercise protected against the initial neurotoxicity from the mAMPH binge or accelerated the repair of the damaged DA terminals. The present experiments were designed to test whether exercise protects against the mAMPH-induced injury. Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an additional week before autoradiographic determination of striatal DAT binding. The autoradiographic findings showed that prior exercise provided no protection against mAMPH-induced damage to striatal DA terminals. These results, together with analyses from our previous experiments, suggest that voluntary exercise may accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise may be useful as therapeutic adjunct in the treatment mAMPH addicts. © 2014 Wiley Periodicals, Inc.

  3. [3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

    International Nuclear Information System (INIS)

    Thompson, J.M.

    1981-01-01

    Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

  4. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [{sup 11}C]raclopride continuous infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. E. [Sungkyunkwon University School of Medicine, Suwon (Korea, Republic of); Cho, S. S.; Choe, Y. S.; Lee, S. Y.; Kang, E.; Kim, B. T. [Seoul National University hospital, Seoul (Korea, Republic of)

    2002-07-01

    In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [{sup 11}C]raclopride PET. Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [{sup 11}C]raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V3', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Striatal V3' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15{+-}6%; putamen, -30{+-}10%). During the 30 min after the game ended, striatal [{sup 11}C]raclopride binding was gradually increased and the V3' approached baseline levels. There was a significant correlation between the reduction in striatal V3' and the task performance during the video game. These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [{sup 11}C]raclopride PET.

  5. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [11C]raclopride continuous infusion

    International Nuclear Information System (INIS)

    Kim, S. E.; Cho, S. S.; Choe, Y. S.; Lee, S. Y.; Kang, E.; Kim, B. T.

    2002-01-01

    In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [ 11 C]raclopride PET. Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [ 11 C]raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V3', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Striatal V3' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15±6%; putamen, -30±10%). During the 30 min after the game ended, striatal [ 11 C]raclopride binding was gradually increased and the V3' approached baseline levels. There was a significant correlation between the reduction in striatal V3' and the task performance during the video game. These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [ 11 C]raclopride PET

  6. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [11C] raclopride continuous infusion

    International Nuclear Information System (INIS)

    Sang Eun Kim; Yearn Seong Choe; Eunjoo Kang; Dong Soo Lee; June-Key Chung; Myung-Chul Lee; Sang Soo Cho

    2004-01-01

    Purpose: In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [ 11 C] raclopride PET. Methods: Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [ 11 C] raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V 3 ', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Results: Striatal V 3 ' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15±6%; putamen, -30±10%). During the 30 min after the game ended, striatal [ 11 C] raclopride binding was gradually increased and the V 3 ' approached baseline levels. There was a significant correlation between the reduction in striatal V 3 ' and the task performance during the video game. Conclusions: These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [ 11 C] raclopride PET. (authors)

  7. No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using (123I)FP-CIT (DaTSCAN) and SPECT

    DEFF Research Database (Denmark)

    Thomsen, G; Knudsen, Gitte Moos; Jensen, PS

    2013-01-01

    BACKGROUND: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like...... receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy...... controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. METHODS: A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present...

  8. Individual differences in the motivation to communicate relate to levels of midbrain and striatal catecholamine markers in male European starlings.

    Science.gov (United States)

    Heimovics, Sarah A; Salvante, Katrina G; Sockman, Keith W; Riters, Lauren V

    2011-11-01

    Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal target, song control region area X, in the regulation of individual differences in the motivation to sing. We used high pressure liquid chromatography with electrochemical detection to measure dopamine, norepinephrine and their metabolites in micropunched samples from VTA, GCt, and area X in male European starlings (Sturnus vulgaris). We categorized males as sexually motivated or non-sexually motivated based on individual differences in song produced in response to a female. Dopamine markers and norepinephrine in VTA and dopamine in area X correlated positively with sexually-motivated song. Norepinephrine in area X correlated negatively with non-sexually-motivated song. Dopamine in GCt correlated negatively with sexually-motivated song, and the metabolite DOPAC correlated positively with non-sexually-motivated song. Results highlight a role for evolutionarily conserved dopaminergic projections from VTA to striatum in the motivation to communicate and highlight novel patterns of catecholamine activity in area X, VTA, and GCt associated with individual differences in sexually-motivated and non-sexually-motivated communication. Correlations between dopamine and norepinephrine markers also suggest that norepinephrine may contribute to individual differences in communication by modifying dopamine neuronal activity in VTA and GCt. Copyright © 2011. Published by Elsevier Inc.

  9. Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome

    Directory of Open Access Journals (Sweden)

    Zhang W

    2016-05-01

    Full Text Available Wen Zhang,1,* Li Wei,2,* Wenjing Yu,1 Xia Cui,1 Xiaofang Liu,2 Qian Wang,1 Sumei Wang2 1Department of Pediatrics, The Third Affiliated Hospital, 2Department of Pediatrics, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Jian-Pi-Zhi-Dong Decoction (JPZDD is a dedicated treatment of Tourette syndrome (TS. The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu and γ-aminobutyric acid (GABA and their receptors in a TS rat model.Materials and methods: Rats were divided into four groups (n=12 each. TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR were observed using Western blot and real-time polymerase chain reaction.Results: Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the m

  10. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

  11. Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

    Science.gov (United States)

    Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

    2014-11-01

    The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  12. Classification of H2O2 as a Neuromodulator that Regulates Striatal Dopamine Release on a Subsecond Time Scale

    Science.gov (United States)

    2012-01-01

    Here we review evidence that the reactive oxygen species, hydrogen peroxide (H2O2), meets the criteria for classification as a neuromodulator through its effects on striatal dopamine (DA) release. This evidence was obtained using fast-scan cyclic voltammetry to detect evoked DA release in striatal slices, along with whole-cell and fluorescence imaging to monitor cellular activity and H2O2 generation in striatal medium spiny neurons (MSNs). The data show that (1) exogenous H2O2 suppresses DA release in dorsal striatum and nucleus accumbens shell and the same effect is seen with elevation of endogenous H2O2 levels; (2) H2O2 is generated downstream from glutamatergic AMPA receptor activation in MSNs, but not DA axons; (3) generation of modulatory H2O2 is activity dependent; (4) H2O2 generated in MSNs diffuses to DA axons to cause transient DA release suppression by activating ATP-sensitive K+ (KATP) channels on DA axons; and (5) the amplitude of H2O2-dependent inhibition of DA release is attenuated by enzymatic degradation of H2O2, but the subsecond time course is determined by H2O2 diffusion rate and/or KATP-channel kinetics. In the dorsal striatum, neuromodulatory H2O2 is an intermediate in the regulation of DA release by the classical neurotransmitters glutamate and GABA, as well as other neuromodulators, including cannabinoids. However, modulatory actions of H2O2 occur in other regions and cell types, as well, consistent with the widespread expression of KATP and other H2O2-sensitive channels throughout the CNS. PMID:23259034

  13. Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.

    Science.gov (United States)

    Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell

    2005-02-08

    The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.

  14. Disease-toxicant interactions in manganese exposed Huntington disease mice: early changes in striatal neuron morphology and dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Jennifer L Madison

    Full Text Available YAC128 Huntington's disease (HD transgenic mice accumulate less manganese (Mn in the striatum relative to wild-type (WT littermates. We hypothesized that Mn and mutant Huntingtin (HTT would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl(2-4H(2O (50 mg/kg on days 0, 3 and 6. Striatal medium spiny neuron (MSN morphology, as well as levels of dopamine (DA and its metabolites (which are known to be sensitive to Mn-exposure, were analyzed at 13 weeks (7 days from initial exposure and 16 weeks (28 days from initial exposure. No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology.

  15. Striatal and extra-striatal dopamine transporter in cannabis and tobacco addiction: a high resolution PET study

    International Nuclear Information System (INIS)

    Leroy, C.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Ribeiro, M.J.; Trichard, Ch.; Karila, L.; Lukasiewicz, M.; Benyamina, A.; Reynaud, M.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Comtat, C.; Artiges, E.; Trichard, Ch.

    2011-01-01

    The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extra-striatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [ 11 C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects. (authors)

  16. Serotonin 2A receptor regulation of striatal neuropeptide gene expression is selective for tachykinin, but not enkephalin neurons following dopamine depletion.

    Science.gov (United States)

    Basura, G J; Walker, P D

    2001-08-15

    Serotonin (5-HT) 2A receptor-mediated regulation of striatal preprotachykinin (PPT) and preproenkephalin (PPE) mRNAs was studied in adult rodents that had been subjected to near-total dopamine (DA) depletion as neonates. Two months following bilateral 6-hydroxydopamine (6-OHDA) lesion, PPT mRNA levels decreased 59-73% across dorsal subregions of the rostral and caudal striatum while PPE transcripts increased 61-94%. Four hours after a single injection of the serotonin 2A/2C receptor agonist, (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1 mg/kg), PPT mRNA expression was significantly increased in DA-depleted rats across all dorsal subregions of the rostral and caudal striatum as compared to 6-OHDA-treated animals alone. In the intact rat, DOI did not influence PPT mRNA levels in the rostral striatum, but did raise expression in the caudal striatum where 5-HT2A receptors are prominent. DOI did not regulate PPE mRNA levels in any striatal sub-region of the intact or DA-depleted rat. Prior administration of the 5-HT2A/2C receptor antagonist, ritanserin (1 mg/kg) or the 5-HT2A receptor antagonist, ketanserin (1 mg/kg) completely blocked the DOI-induced increases in striatal PPT mRNA in both lesioned and intact animals. The ability of ketanserin to produce identical results as ritanserin suggests that 5-HT2A receptor-mediated regulation is selectively strengthened within tachykinin neurons of the rostral striatum which are suppressed by DA depletion. The selectivity suggests that 5-HT2A receptor upregulation following DA depletion is capable of regulating tachykinin biosynthesis without influencing enkephalin expression in striatal output neurons.

  17. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  18. Dysregulation of striatal projection neurons in Parkinson's disease.

    Science.gov (United States)

    Beck, Goichi; Singh, Arun; Papa, Stella M

    2018-03-01

    The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

  19. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    International Nuclear Information System (INIS)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging

  20. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

  1. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Walters, Jennifer L.; Lansdell, Theresa A.; Lookingland, Keith J.; Baker, Lisa E.

    2015-01-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. - Highlights: • Male rats received gestational and chronic exposure to ATZ (10 mg/kg and 100 μg/kg). • ATZ altered locomotor activity and impaired motor coordination. • ATZ lowered striatal DA and DOPAC concentrations. • ATZ produced a potential anxiogenic effect. • ATZ did not impair performance in learning and memory assessments.

  2. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walters, Jennifer L., E-mail: Jennifer.l.walters@wmich.edu [Western Michigan University, Department of Psychology, 1903 W Michigan Ave, Kalamazoo, MI 49008-5439 (United States); Lansdell, Theresa A., E-mail: lansdel1@msu.edu [Michigan State University, Department of Pharmacology and Toxicology, 1355 Bogue Street, East Lansing, MI 48824 (United States); Lookingland, Keith J., E-mail: lookingl@msu.edu [Michigan State University, Department of Pharmacology and Toxicology, 1355 Bogue Street, East Lansing, MI 48824 (United States); Baker, Lisa E., E-mail: lisa.baker@wmich.edu [Western Michigan University, Department of Psychology, 1903 W Michigan Ave, Kalamazoo, MI 49008-5439 (United States)

    2015-12-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. - Highlights: • Male rats received gestational and chronic exposure to ATZ (10 mg/kg and 100 μg/kg). • ATZ altered locomotor activity and impaired motor coordination. • ATZ lowered striatal DA and DOPAC concentrations. • ATZ produced a potential anxiogenic effect. • ATZ did not impair performance in learning and memory assessments.

  3. Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

    Science.gov (United States)

    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

    Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include

  4. Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding.

    Directory of Open Access Journals (Sweden)

    Nicole Speed

    Full Text Available The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt involved in insulin signaling induced by exposure to a high-fat (HF diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT. Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food

  5. Stimulated serotonin release from hyperinnervated terminals subsequent to neonatal dopamine depletion regulates striatal tachykinin, but not enkephalin gene expression.

    Science.gov (United States)

    Basura, G J; Walker, P D

    2000-09-30

    Dopamine (DA) depletion in neonatal rodents results in depressed tachykinin and elevated enkephalin gene expression in the adult striatum (STR). Concurrently, serotonin (5-HT) fibers sprout to hyperinnervate the DA-depleted anterior striatum (A-STR). The present study was designed to determine if increased 5-HT release from sprouted terminals influences dysregulated preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the DA-depleted STR. Three-day-old Sprague-Dawley rat pups received bilateral intracerebroventricular injections of vehicle or the DA neurotoxin 6-hydroxydopamine (6-OHDA, 100 microg). Two months later, rats received a single intraperitoneal injection of vehicle or the acute 5-HT releasing agent p-chloroamphetamine (PCA; 10 mg/kg). Rats were killed 4 h later and striata processed for monoamine content by HPLC-ED and mRNA expression by in situ hybridization within specific subregions of the A-STR and posterior striatum (P-STR). 6-OHDA treatment severely (>98%) reduced striatal DA levels, while 5-HT content in the A-STR was significantly elevated (doubled), indicative of 5-HT hyperinnervation. Following 6-OHDA, PPT mRNA levels were depressed 60-66% across three subregions of the A-STR and 52-59% across two subregions of the P-STR, while PPE mRNA expression was elevated in both the A-STR (50-62%) and P-STR (55-82%). PCA normalized PPT mRNA levels in all regions of the DA-depleted A-STR and P-STR, yet did not alter PPE levels in either dorsal central or medial regions from 6-OHDA alone, but reduced PPE to control levels in the dorsal lateral A-STR. These data indicate that increased 5-HT neurotransmission, following neonatal 6-OHDA treatment, primarily influences PPT-containing neurons of the direct striatal output pathway.

  6. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

    Science.gov (United States)

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-10-11

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

  7. Does human presynaptic striatal dopamine function predict social conformity?

    Science.gov (United States)

    Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

    2014-03-01

    Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

  8. Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Bruno, J P; Byrnes, E M; Johnson, B J

    1995-11-01

    The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

  9. A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice.

    Directory of Open Access Journals (Sweden)

    Alexander Kurz

    2010-07-01

    Full Text Available Parkinson's disease (PD, the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA. PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons.Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD was absent in corticostriatal slices from old transgenic mice.Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches.

  10. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    International Nuclear Information System (INIS)

    Asensio, S.; Goldstein, R.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F.; Volkow, N.D.; Goldstein, R.Z.

    2010-01-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with ( 11 C)raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  11. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Energy Technology Data Exchange (ETDEWEB)

    Asensio, S.; Goldstein, R.; Asensio, S.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F..; Volkow, N.D.; Goldstein, R.Z.

    2010-05-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  12. Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

    Directory of Open Access Journals (Sweden)

    Nicola J Platt

    Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

  13. Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

    Science.gov (United States)

    Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

    2017-07-01

    Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

  14. [Effects of acupuncture stimulation of different acupoint groups on sleeping duration and serum and striatal dopamine contents in rats with gastric mucosal injury].

    Science.gov (United States)

    Yang, Ping; Peng, Lei; Li, Jie-Ting; Ma, Hui-Fang

    2014-02-01

    To observe the effect of acupuncture intervention on gastric ulcer (GU) and sleeping quality from the viewpoint of brain-gut axis which plays an important role in the regulation of many vital functions in health and disease. Forty male Wistar rats were randomized into normal control, GU model, acupuncture of "Zhongwan" (CV 12)-"Zusanli" (ST 36, gastric treatment acupoints), acupuncture of "Shenmai" (BL 62)-"Zhaohai" (KI 6, sleep-promotion acupoints), and acupuncture of CV 12-ST 36-BL 62-KI 6 (combined treatment) groups, with 8 rats in each group. GU model was established by intragastric perfusion of dehydrated alcohol (1 mL/rat), and sleep model established by intraperitoneal injection of pentobarbital sodium (40 mg/kg) after the last treatment. The abovementioned acupoints were punctured with filiform needles and stimulated by manipulating the needle for about 30 s, once every 5 mm during 20 mm of needle retention. The treatment was conducted once daily for five days. Gastric mucosal lesion index was assessed by Guth's method, and the mucosal pathological changes were observed under microscope after H. E. staining. The contents of dopamine (DA) in the serum and striatal tissues were detected by ELISA kit. Compared with the normal control group, the rats' sleeping duration, and serum DA content were markedly decreased and the gastric mucosal lesion index, and the striatal DA content remarkably increased in the model group (P sleeping duration, and serum DA content were significantly increased, and the gastric mucosal lesion index, and the striatal DA content remarkably down-regulated in the CV 12-ST 36 (gastric treatment acupoints), BL 62-KI 6 (sleep-promotion acupoints) and CV 12-ST 36-BL 62-KI 6 (combined treatment) groups (P sleep promotion acupoints group in reducing mucosal lesion index and in increasing serum DA level (P sleeping duration in gastric lesion rats, which may be related to its effects in increasing blood DA and lowering striatal DA level

  15. Molecular substrates of action control in cortico-striatal circuits.

    Science.gov (United States)

    Shiflett, Michael W; Balleine, Bernard W

    2011-09-15

    The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, G L; Szabo, G; Telegdy, G [Institute of Pathophysiology, University Medical School, Szeged, Hungary; Penke, B [Institute of Medical Chemistry, University Medical School, Szeged, Hungary

    1981-01-29

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of ..cap alpha..-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of (/sup 3/H)DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10/sup -5/ M). Potassium-induced in vitro release of (/sup 3/H)DA from striatal slices was significantly increased by 10/sup -5/ M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

  17. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    International Nuclear Information System (INIS)

    Kovacs, G.L.; Szabo, G.; Telegdy, G.; Penke, B.

    1981-01-01

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of α-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [ 3 H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10 -5 M). Potassium-induced in vitro release of [ 3 H]DA from striatal slices was significantly increased by 10 -5 M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions. (Auth.)

  18. Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Zwiers, Marcel P.; Forde, Natalie J.; Williams, Steven C. R.; Durston, Sarah; Brandeis, Daniel; Glennon, Jeffrey C.; Franke, Barbara; Lythgoe, David J.; Buitelaar, Jan K.

    Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We

  19. Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

    DEFF Research Database (Denmark)

    Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N

    2004-01-01

    (DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported...

  20. Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients.

    Science.gov (United States)

    de la Fuente-Sandoval, Camilo; Reyes-Madrigal, Francisco; Mao, Xiangling; León-Ortiz, Pablo; Rodríguez-Mayoral, Oscar; Jung-Cook, Helgi; Solís-Vivanco, Rodolfo; Graff-Guerrero, Ariel; Shungu, Dikoma C

    2018-03-15

    Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-11-01

    Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  3. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  4. Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

    Science.gov (United States)

    Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

    2014-12-01

    Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic

  5. Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

    International Nuclear Information System (INIS)

    Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

    1988-01-01

    Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

  6. Evaluation of the effects and mechanisms of action of glufosinate, an organophosphate insecticide, on striatal dopamine release by using in vivo microdialysis in freely moving rats.

    Science.gov (United States)

    Ferreira Nunes, Brenda V; Durán, Rafael; Alfonso, Miguel; de Oliveira, Iris Machado; Ferreira Faro, Lilian R

    2010-10-01

    The purpose of the present work was to assess the effects of glufosinate ammonium (GLA), an aminoacid structurally related to glutamate, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to HPLC-EC. Intrastriatal administration of GLA produced significant concentration-dependent increases in DA levels. At least two mechanisms can be proposed to explain these increases: GLA could be inducing DA release from synaptic vesicles or producing an inhibition of DA transporter (DAT). Thus, we investigated the effects of GLA under Ca(++)-free condition, and after pretreatment with reserpine and TTX. It was observed that the pretreatment with Ca(++)-free Ringer, reserpine or TTX significantly reduced the DA release induced by GLA. Coinfusion of GLA and nomifensine shows that the GLA-induced DA release did not involve the DAT. These results show that GLA-induced striatal DA release is probably mediated by an exocytotic-, Ca(++)-, action potential-dependent mechanism, being independent of DAT.

  7. Free radical production induced by methamphetamine in rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Pubill, David; Chipana, Carlos; Camins, Antonio; Pallas, Merce; Camarasa, Jordi; Escubedo, Elena

    2005-01-01

    The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 μM) prevented METH-induced ROS production, thus implicating calcium and α7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 μM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 μM) for 30 min reduced [ 3 H]DA uptake by 60%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of α 7 nicotinic receptors and Ca 2+ entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates α 7 nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca 2+ . This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA

  8. Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

    Science.gov (United States)

    de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

    2016-01-01

    Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally

  9. The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

    2017-01-01

    Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener ...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

  10. Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Johnson, B J; Bruno, J P

    1995-02-01

    A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

  11. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

    Directory of Open Access Journals (Sweden)

    Maria A de Souza Silva

    2016-04-01

    Full Text Available Purpose: Dopamine (DA, which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA, nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered intranasal application of 3 mg/kg IN-DA and vehicle (VEH, with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT two hours following administration of the radioligand. Results: 1 After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered dopamine had central action and increased DA levels comparable to that found previously with L-DOPA administration. 2 DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant

  12. D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

    Science.gov (United States)

    Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

    2011-02-14

    Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  14. 125I-β-CIT imaging study of striatal dopamine transporters in mice model of parkinsonism

    International Nuclear Information System (INIS)

    Liu Zhenguo; Sun Wenshan; Weng Zhongfang; Chen Shengdi; Shen Minghua; Zhu Chengmo

    2001-01-01

    Objective: To detect the activity of striatal dopamine transporters (DAT) in lesions of different order of severity of MPTP-induced mice model of parkinsonism by autoradiography with 125 I-β-CIT and to evaluate the clinical use of the β-CIT imaging for DAT detection. Methods: With regard to the different duration (days) of MPTP treatment, the C57BL mice were randomly divided into 5 groups, that is MPTP 1, 3, 5 and 7 day groups and control group treated with normal saline instead of MPTP. Two hours after intravenous administration with 125 I-β-CIT of 148 kBq, the brain tissue sections were imaged by autoradiography. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electrochemical detection (HPLC-ECD). The tyrosine hydroxylase (TH)-positive cells and fibres in the substantia nigra and striatum of the mice were observed by means of immunohistochemical technique. Results: As compared with control group, the radioactivity ratios of striatum to cortex (ST/CX) in 4 MPTP-treated groups were significantly reduced, by 20%, 42%, 45% and 52%, respectively. The concentrations of DA in the striatum of 4 MPTP-treated groups were remarkably decreased, by 47%, 75%, 95% and 95%, respectively. The gradual loss of DA neurons and fibres in the substantia nigra and striatum in 4 MPTP-treated groups was observed under microscopy. Conclusions: The functional abnormality of DAT paralleled the changes observed in neurochemistry and neuropathology studies in the lesions of different order of injury of the MPTP-treated mice. The β-CIT scanning for the activity of DAT may be useful for diagnosing PD at earlier phase and for monitoring the progression of the disease

  15. Behavioral sensitivity of temporally modulated striatal neurons

    Directory of Open Access Journals (Sweden)

    George ePortugal

    2011-07-01

    Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

  16. A new framework for cortico-striatal plasticity: behavioural theory meets in vitro data at the reinforcement-action interface.

    Directory of Open Access Journals (Sweden)

    Kevin N Gurney

    2015-01-01

    Full Text Available Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface. Much evidence suggests that this occurs when phasic dopamine, acting as a reinforcement prediction error, gates plasticity at cortico-striatal synapses, and thereby changes the future likelihood of selecting the action(s coded by striatal neurons. But this hypothesis faces serious challenges. First, cortico-striatal plasticity is inexplicably complex, depending on spike timing, dopamine level, and dopamine receptor type. Second, there is a credit assignment problem-action selection signals occur long before the consequent dopamine reinforcement signal. Third, the two types of striatal output neuron have apparently opposite effects on action selection. Whether these factors rule out the interface hypothesis and how they interact to produce reinforcement learning is unknown. We present a computational framework that addresses these challenges. We first predict the expected activity changes over an operant task for both types of action-coding striatal neuron, and show they co-operate to promote action selection in learning and compete to promote action suppression in extinction. Separately, we derive a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then show this model produces the predicted activity changes necessary for learning and extinction in an operant task, a remarkable convergence of a bottom-up data-driven plasticity model with the top-down behavioural requirements of learning theory. Moreover, we show the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. Validating the model, we show it can account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. By bridging the levels between the single synapse and

  17. Modification of the striatal dopaminergic neuron system by carbon monoxide exposure in free-moving rats, as determined by in vivo brain microdialysis

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Shuichi; Kurosaki, Kunihiko; Kuriiwa, Fumi; Endo, Takahiko [Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Mukai, Toshiji [Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-0015 (Japan)

    2002-10-01

    Acute carbon monoxide (CO) intoxication in humans results in motor deficits, which resemble those in Parkinson's disease, suggesting possible disturbance of the central dopaminergic (DAergic) neuronal system by CO exposure. In the present study, therefore, we explored the effects of CO exposure on the DAergic neuronal system in the striatum of freely moving rats by means of in vivo brain microdialysis. Exposure of rats to CO (up to 0.3%) for 40 min caused an increase in extracellular dopamine (DA) levels and a decrease in extracellular levels of its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum depending on the CO concentration. Reoxygenation following termination of the CO exposure resulted in a decline of DA to the control level and an overshoot in the recovery of DOPAC and HVA to levels higher than the control. A monoamine oxidase type A (MAO-A) inhibitor, clorgyline, significantly potentiated the CO-induced increase in DA and completely abolished the subsequent overshoot in the recovery of DOPAC and HVA. Tetrodotoxin, a Na{sup +} channel blocker, completely abolished both the CO-induced increase in DA and the overshoot of DOPAC and HVA. A DA uptake inhibitor, nomifensine, strongly potentiated the CO-induced increase in DA without affecting the subsequent overshoot of DOPAC and HVA. Clorgyline further potentiated the effect of nomifensine on the CO-induced increase in DA, although a slight overshoot of DOPAC and HVA appeared. These findings suggest that (1) CO exposure may stimulate Na{sup +}-dependent DA release in addition to suppressing DA metabolism, resulting in a marked increase in extracellular DA in rat striatum, and (2) CO withdrawal and subsequent reoxygenation may enhance the oxidative metabolism, preferentially mediated by MAO-A, of the increased extracellular DA. In the light of the neurotoxicity of DA per se and reactive substances, such as quinones and activated oxygen species

  18. Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

    Science.gov (United States)

    Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

    1996-04-01

    Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

  19. Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia.

    Science.gov (United States)

    Horga, Guillermo; Cassidy, Clifford M; Xu, Xiaoyan; Moore, Holly; Slifstein, Mark; Van Snellenberg, Jared X; Abi-Dargham, Anissa

    2016-08-01

    (50%) were female. Of the controls (mean [SEM] age, 33.7 [8.8] years), 10 (42%) were male and 14 (58%) were female. Patients had an abnormal pattern of striatal connectivity, which included abnormal caudate connections with a distributed set of associative cortex regions (χ229 = 53.55, P = .004). In patients, more deviation from the multivariate pattern of striatal connectivity found in controls correlated specifically with more severe positive symptoms (ρ = -0.77, P = .002). Striatal connectivity also correlated with baseline binding potential across cortical and extrastriatal subcortical regions (t25 = 3.01, P = .01, Bonferroni corrected) but not with its change after amphetamine administration. Using a multimodal, circuit-level interrogation of striatal-cortical connections, it was demonstrated that the functional topography of these connections is globally disrupted in unmedicated patients with schizophrenia. These findings suggest that striatal-cortical dysconnectivity may underlie the effects of dopamine dysregulation on the pathophysiologic mechanism of psychotic symptoms.

  20. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

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    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  1. Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

    Science.gov (United States)

    Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

    2013-01-01

    Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

  2. PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 mice.

    Science.gov (United States)

    Perez, Virgili; Unzeta, Mercedes

    2003-02-01

    Monoamine oxidase isoform B (MAO-B) is involved in Parkinson's disease (PD) induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxin (MPTP) in human and non-human-primate. MAO-B inhibitors, such as L-deprenyl have shown to prevent against MPTP-toxicity in different species, and it has been used in Parkinson therapy, however, the fact that it is metabolized to (-)-methamphetamine and (-)-amphetamine highlights the need to find out new MAO-B inhibitors without a structural amphetaminic moiety. In this context we herein report, for the first time, anywhere a novel non-amphetamine-like MAO-B inhibitor, PF 9601N, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine. This attenuates the MPTP-induced striatal dopamine depletion in young-adult and adult-old C57/BL mice, using different schedules of administration, and which behave "ex vivo" as a slightly more potent and selective MAO-B inhibitor than L-deprenyl, assayed for comparative purposes in the same experimental conditions. The MAO-B ID(50) values were calculated from the total MAO-B activity measured against [14C] phenylethylamine (22 microM) as substrate, at each inhibitor concentration. The MAO-B ID(50) values resulted to be 381 and 577 nmol/kg for PF 9601N and L-deprenyl, respectively. The intraperitoneally (i.p.) co-administration to young-adult C57/BL6 mice of MPTP (30 mg/kg), with different concentrations of PF 9601N or L-deprenyl (29.5-0.357 micromol/kg) showed a dose-dependent protective effect against striatal dopamine depletion, measuring the dopamine contents and its metabolites by HPLC. The ED(50) value proved to be 3.07 micromol/kg without any significant differences between either MAO-B inhibitor. Nevertheless, lower doses of PF 9601N (1.5 micromol/kg) were necessary to get almost total protection, without any change in the DOPAC and HVA content, when administered 2 h before MPTP (30 mg/kg), whereas partial protection (45%) against dopamine depletion was observed in the case of L-deprenyl. In

  3. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  4. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

    Science.gov (United States)

    Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

    2015-08-01

    Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

  5. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

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    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  6. Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

    Science.gov (United States)

    Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

    2016-08-23

    Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

  7. Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors.

    Science.gov (United States)

    Suda, Yukari; Kuzumaki, Naoko; Narita, Michiko; Hamada, Yusuke; Shibasaki, Masahiro; Tanaka, Kenichi; Tamura, Hideki; Kawamura, Takashi; Kondo, Takashige; Yamanaka, Akihiro; Narita, Minoru

    2018-02-19

    Ghrelin plays roles in a wide range of central functions by activating the growth hormone secretagogue receptor (GHSR). This receptor has recently been found in the substantia nigra (SN) to control dopamine (DA)-related physiological functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the consequent depletion of striatal DA are known to underlie the motor deficits observed in Parkinson's disease (PD). In the present study, we further investigated the role of the SN-ghrelin system in motor function under the stereotaxic injection of AAV-CMV-FLEX-diphtheria toxin A (DTA) into the SN of dopamine transporter (DAT)-Cre (DAT SN ::DTA) mice to expunge DA neurons of the SNc. First, we confirmed the dominant expression of GHSR1a, which is a functional GHSR, in tyrosine hydroxylase (TH)-positive DA neurons in the SNc of control mice. In DAT SN ::DTA mice, we clearly observed motor dysfunction using several behavioral tests. An immunohistochemical study revealed a dramatic loss of TH-positive DA neurons in the SNc and DAT-labeled axon terminals in the striatum, and an absence of mRNAs for TH and DAT in the SN of DAT SN ::DTA mice. The mRNA level of GHSR1a was drastically decreased in the SN of these mice. In normal mice, we also found the mRNA expression of GHSR1a within GABAergic neurons in the SN pars reticulata (SNr). Under these conditions, a single injection of ghrelin into the SN failed to improve the motor deficits caused by ablation of the nigrostriatal DA network using DAT SN ::DTA mice, whereas intra-SN injection of ghrelin suppressed the motor dysfunction caused by the administration of haloperidol, which is associated with the transient inhibition of DA transmission. These findings suggest that phasic activation of the SNc-ghrelin system could improve the dysregulation of nigrostriatal DA transmission related to the initial stage of PD, but not the motor deficits under the depletion of nigrostriatal DA. Although GHSRs are found in non-DA

  8. Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-10-15

    Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

  9. Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

    Science.gov (United States)

    Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

    2017-01-01

    Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602

  10. Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

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    Adriani Walter

    2012-11-01

    Full Text Available Abstract Background Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD and obsessive-compulsive disorder (OCD. Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype. Methods Male CD-1 mice were immunized with DAT peptide fragments (DAT-i, or vehicle alone (VEH, to generate elevated circulating levels of DAT auto-antibodies (aAbs. Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec, mice had a choice between either an immediate small amount of food (SS, or a larger amount of food after a delay (LL, which increased progressively across sessions (from 0 to 150 sec. Results DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest. Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. Conclusions Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization

  11. Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates.

    Science.gov (United States)

    Singh, Arun; Jenkins, Meagan A; Burke, Kenneth J; Beck, Goichi; Jenkins, Andrew; Scimemi, Annalisa; Traynelis, Stephen F; Papa, Stella M

    2018-01-23

    Dopamine (DA) loss in Parkinson's disease (PD) alters the function of striatal projection neurons (SPNs) and causes motor deficits, but DA replacement can induce further abnormalities. A key pathological change in animal models and patients is SPN hyperactivity; however, the role of glutamate in altered DA responses remains elusive. We tested the effect of locally applied AMPAR or NMDAR antagonists on glutamatergic signaling in SPNs of parkinsonian primates. Following a reduction in basal hyperactivity by antagonists at either receptor, DA inputs induced SPN firing changes that were stable during the entire motor response, in clear contrast with the typically unstable effects. The SPN activity reduction over an extended putamenal area controlled the release of involuntary movements in the "on" state and therefore improved motor responses to DA replacement. These results demonstrate the pathophysiological role of upregulated SPN activity and support strategies to reduce striatal glutamate signaling for PD therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Striatal dysfunction in attention deficit and hyperkinetic disorder

    International Nuclear Information System (INIS)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

  13. Assessment of striatal & postural deformities in patients with Parkinson's disease

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    Sanjay Pandey

    2016-01-01

    Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

  14. Striatal dysfunction in attention deficit and hyperkinetic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

  15. Prefrontal cortex and striatal activation by feedback in Parkinson's disease

    NARCIS (Netherlands)

    Keitz, Martijn; Koerts, Janneke; Kortekaas, Rudie; Renken, Remco; de Jong, Bauke M.; Leenders, Klaus L.

    2008-01-01

    Positive feedbacks reinforce goal-directed behavior and evoke pleasure. in Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary

  16. Ventral striatal activity correlates with memory confidence for old- and new-responses in a difficult recognition test.

    Directory of Open Access Journals (Sweden)

    Ulrike Schwarze

    Full Text Available Activity in the ventral striatum has frequently been associated with retrieval success, i.e., it is higher for hits than correct rejections. Based on the prominent role of the ventral striatum in the reward circuit, its activity has been interpreted to reflect the higher subjective value of hits compared to correct rejections in standard recognition tests. This hypothesis was supported by a recent study showing that ventral striatal activity is higher for correct rejections than hits when the value of rejections is increased by external incentives. These findings imply that the striatal response during recognition is context-sensitive and modulated by the adaptive significance of "oldness" or "newness" to the current goals. The present study is based on the idea that not only external incentives, but also other deviations from standard recognition tests which affect the subjective value of specific response types should modulate striatal activity. Therefore, we explored ventral striatal activity in an unusually difficult recognition test that was characterized by low levels of confidence and accuracy. Based on the human uncertainty aversion, in such a recognition context, the subjective value of all high confident decisions is expected to be higher than usual, i.e., also rejecting items with high certainty is deemed rewarding. In an accompanying behavioural experiment, participants rated the pleasantness of each recognition response. As hypothesized, ventral striatal activity correlated in the current unusually difficult recognition test not only with retrieval success, but also with confidence. Moreover, participants indicated that they were more satisfied by higher confidence in addition to perceived oldness of an item. Taken together, the results are in line with the hypothesis that ventral striatal activity during recognition codes the subjective value of different response types that is modulated by the context of the recognition test.

  17. Global actions of nicotine on the striatal microcircuit

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    Victor E Plata

    2013-11-01

    Full Text Available The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA, the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  18. Global actions of nicotine on the striatal microcircuit.

    Science.gov (United States)

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

    2013-01-01

    what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  19. DISC1 and striatal volume: a potential risk phenotype for mental illness

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    M. Mallar eChakravarty

    2012-06-01

    Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

  20. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

    International Nuclear Information System (INIS)

    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho; Seppaenen, Marko; Noponen, Tommi

    2014-01-01

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [ 123 I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  1. Anatomical and electrophysiological changes in striatal TH interneurons after loss of the nigrostriatal dopaminergic pathway.

    Science.gov (United States)

    Ünal, Bengi; Shah, Fulva; Kothari, Janish; Tepper, James M

    2015-01-01

    Using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the tyrosine hydroxylase (TH) promoter, we have previously shown that there are approximately 3,000 striatal EGFP-TH interneurons per hemisphere in mice. Here, we report that striatal TH-EGFP interneurons exhibit a small, transient but significant increase in number after unilateral destruction of the nigrostriatal dopaminergic pathway. The increase in cell number is accompanied by electrophysiological and morphological changes. The intrinsic electrophysiological properties of EGFP-TH interneurons ipsilateral to 6-OHDA lesion were similar to those originally reported in intact mice except for a significant reduction in the duration of a characteristic depolarization induced plateau potential. There was a significant change in the distribution of the four previously described electrophysiologically distinct subtypes of striatal TH interneurons. There was a concomitant increase in the frequency of both spontaneous excitatory and inhibitory post-synaptic currents, while their amplitudes did not change. Nigrostriatal lesions did not affect somatic size or dendritic length or branching, but resulted in an increase in the density of proximal dendritic spines and spine-like appendages in EGFP-TH interneurons. The changes indicate that electrophysiology properties and morphology of striatal EGFP-TH interneurons depend on endogenous levels of dopamine arising from the nigrostriatal pathway. Furthermore, these changes may serve to help compensate for the changes in activity of spiny projection neurons that occur following loss of the nigrostriatal innervation in experimental or in early idiopathic Parkinson's disease by increasing feedforward GABAergic inhibition exerted by these interneurons.

  2. Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder

    Directory of Open Access Journals (Sweden)

    Haifeng Hou

    2012-01-01

    Full Text Available In recent years, internet addiction disorder (IAD has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT levels measured by T99mc-TRODAT-1 single photon emission computed tomography (SPECT brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V and weight (W of bilateral corpus striatum as well as the T99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

  3. Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling.

    Science.gov (United States)

    Schuweiler, D R; Athens, J M; Thompson, J M; Vazhayil, S T; Garris, P A

    2018-01-15

    Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Motor Skill Learning Is Associated with Phase-Dependent Modifications in the Striatal cAMP/PKA/DARPP-32 Signaling Pathway in Rodents.

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    Yu Qian

    Full Text Available Abundant evidence points to a key role of dopamine in motor skill learning, although the underlying cellular and molecular mechanisms are still poorly understood. Here, we used a skilled-reaching paradigm to first examine changes in the expression of the plasticity-related gene Arc to map activity in cortico-striatal circuitry during different phases of motor skill learning in young animals. In the early phase, Arc mRNA was significantly induced in the medial prefrontal cortex (mPFC, cingulate cortex, primary motor cortex, and striatum. In the late phase, expression of Arc did not change in most regions, except in the mPFC and dorsal striatum. In the second series of experiments, we studied the learning-induced changes in the phosphorylation state of dopamine and cAMP-regulated phosphoprotein, 32k Da (DARPP-32. Western blot analysis of the phosphorylation state of DARPP-32 and its downstream target cAMP response element-binding protein (CREB in the striatum revealed that the early, but not late, phase of motor skill learning was associated with increased levels of phospho-Thr34-DARPP-32 and phospho-Ser133-CREB. Finally, we used the DARPP-32 knock-in mice with a point mutation in the Thr34 regulatory site (i.e., protein kinase A site to test the significance of this pathway in motor skill learning. In accordance with our hypothesis, inhibition of DARPP-32 activity at the Thr34 regulatory site strongly attenuated the motor learning rate and skilled reaching performance of mice. These findings suggest that the cAMP/PKA/DARPP-32 signaling pathway is critically involved in the acquisition of novel motor skills, and also demonstrate a dynamic shift in the contribution of cortico-striatal circuitry during different phases of motor skill learning.

  5. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

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    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  6. Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine.

    Directory of Open Access Journals (Sweden)

    Henrike Planert

    Full Text Available D1 and D2 receptor expressing striatal medium spiny neurons (MSNs are ascribed to striatonigral ("direct" and striatopallidal ("indirect" pathways, respectively, that are believed to function antagonistically in motor control. Glutamatergic synaptic transmission onto the two types is differentially affected by Dopamine (DA, however, less is known about the effects on MSN intrinsic electrical properties. Using patch clamp recordings, we comprehensively characterized the two pathways in rats and mice, and investigated their DA modulation. We identified the direct pathway by retrograde labeling in rats, and in mice we used transgenic animals in which EGFP is expressed in D1 MSNs. MSNs were subjected to a series of current injections to pinpoint differences between the populations, and in mice also following bath application of DA. In both animal models, most electrical properties were similar, however, membrane excitability as measured by step and ramp current injections consistently differed, with direct pathway MSNs being less excitable than their counterparts. DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences. Pronounced changes in AP shape were seen in D2 MSNs. In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors. Thus, DA induced changes in excitability were D1 R mediated and intrinsic to direct pathway MSNs, and not a secondary network effect of altered synaptic transmission. DAergic modulation of intrinsic properties therefore acts in a synergistic manner with previously reported effects of DA on afferent synaptic transmission and dendritic processing, supporting the antagonistic model for direct vs. indirect striatal pathway function.

  7. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

    Science.gov (United States)

    Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

    2017-10-11

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

  8. Reduced striatal D2 receptor binding in myoclonus-dystonia

    International Nuclear Information System (INIS)

    Beukers, R.J.; Weisscher, N.; Tijssen, M.A.J.; Booij, J.; Zijlstra, F.; Amelsvoort, T.A.M.J. van

    2009-01-01

    To study striatal dopamine D 2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using 123 I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D 2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. (orig.)

  9. No association between striatal dopamine transporter binding and body mass index

    DEFF Research Database (Denmark)

    van de Giessen, Elsmarieke; Hesse, Swen; Caan, Matthan W A

    2013-01-01

    Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine...... transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated....

  10. Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

    Science.gov (United States)

    Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

    2017-06-30

    Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

  11. Release of [3H]-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

    International Nuclear Information System (INIS)

    Levin, J.A.; Schmidt, C.J.; Lovenberg, W.

    1986-01-01

    MDMA is a phenylisopropylamine which is reported to have unique behavioral effects in man. Because of its structural similarities to the amphetamines the authors have compared the effects of MDMA and two related amphetamines on the spontaneous release of tritiated dopamine (DA) and serotonin (5HT) from superfused rat striatal slices. At concentrations of 10 -7 - 10 -5 M MDMA and the serotonergic neurotoxin, p-chloroamphetamine, were equipotent releasers of [ 3 H]5HT being approximately 10x more potent than methamphetamine. However, methamphetamine was the more potent releaser of [ 3 H]DA by a factor of approximately 10x. MDMA-induced release of both [ 5 H]5HT and [ 3 H]DA was Ca 2+ -independent and inhibited by selective monoamine uptake blockers suggesting a carrier-dependent release mechanism. Synaptosomal uptake experiments with (+)[ 3 H]MDMA indicated no specific uptake of the drug further suggesting the effect of uptake blockers may be to inhibit the carrier-mediated export of amines displaced by MDMA

  12. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Hansen, Freja Herborg; Sørensen, Gunnar

    2013-01-01

    believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine......The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence...... transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization...

  13. Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

    Science.gov (United States)

    Nazari, Qand Agha; Kume, Toshiaki; Izuo, Naotaka; Takada-Takatori, Yuki; Imaizumi, Atsushi; Hashimoto, Tadashi; Izumi, Yasuhiko; Akaike, Akinori

    2013-01-01

    Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

  14. Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

    Science.gov (United States)

    Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

    2014-09-01

    Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  15. Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's disease patients

    International Nuclear Information System (INIS)

    Chang Icheng; Lue Kunhan; Hsieh Hungjen; Liu Shuhsin; Kao, Chinhao K.

    2011-01-01

    6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. (author)

  16. Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

    Directory of Open Access Journals (Sweden)

    Mathieu Baudonnat

    2017-05-01

    Full Text Available Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R learning critically depends on the dorsal striatum (DS, spatial memory relies on the hippocampus (HPC. Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments.

  17. Arc mRNA induction in striatal efferent neurons associated with response learning.

    Science.gov (United States)

    Daberkow, D P; Riedy, M D; Kesner, R P; Keefe, K A

    2007-07-01

    The dorsal striatum is involved in motor-response learning, but the extent to which distinct populations of striatal efferent neurons are differentially involved in such learning is unknown. Activity-regulated, cytoskeleton-associated (Arc) protein is an effector immediate-early gene implicated in synaptic plasticity. We examined arc mRNA expression in striatopallidal vs. striatonigral efferent neurons in dorsomedial and dorsolateral striatum of rats engaged in reversal learning on a T-maze motor-response task. Male Sprague-Dawley rats learned to turn right or left for 3 days. Half of the rats then underwent reversal training. The remaining rats were yoked to rats undergoing reversal training, such that they ran the same number of trials but ran them as continued-acquisition trials. Brains were removed and processed using double-label fluorescent in situ hybridization for arc and preproenkephalin (PPE) mRNA. In the reversal, but not the continued-acquisition, group there was a significant relation between the overall arc mRNA signal in dorsomedial striatum and the number of trials run, with rats reaching criterion in fewer trials having higher levels of arc mRNA expression. A similar relation was seen between the numbers of PPE(+) and PPE(-) neurons in dorsomedial striatum with cytoplasmic arc mRNA expression. Interestingly, in behaviourally activated animals significantly more PPE(-) neurons had cytoplasmic arc mRNA expression. These data suggest that Arc in both striatonigral and striatopallidal efferent neurons is involved in striatal synaptic plasticity mediating motor-response learning in the T-maze and that there is differential processing of arc mRNA in distinct subpopulations of striatal efferent neurons.

  18. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  19. Levodopa administration modulates striatal processing of punishment-associated items in healthy participants.

    Science.gov (United States)

    Wittmann, Bianca C; D'Esposito, Mark

    2015-01-01

    Appetitive and aversive processes share a number of features such as their relevance for action and learning. On a neural level, reward and its predictors are associated with increased firing of dopaminergic neurons, whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission. Recent data indicate, however, that the dopaminergic system also responds to aversive stimuli and associated actions. In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans. Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks. Levodopa administration increased striatal activations for cues presented in punishment blocks. In an interaction with individual personality scores, levodopa also enhanced striatal activation for punishment-predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension. These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation. These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum, suggesting an optimal level of dopamine release for motivational processing.

  20. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

    DEFF Research Database (Denmark)

    Storgaard, J; Kornblit, B T; Zimmer, J

    2000-01-01

    of lactate dehydrogenase in the medium and glutamic acid decarboxylase in tissue homogenates. 3-NPA toxicity (25-100 microM in 5 mM glucose, 24-48 h) appeared to be highly dependent on culture medium glucose levels. 3-NPA treatment caused also a dose-dependent lactate increase, reaching a maximum......Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay...... of threefold increase above control at 100 microM. Both a high dose of glutamate (5 mM) and glutamate uptake blockade by dl-threo-beta-hydroxyaspartate potentiated 3-NPA neurotoxicity in corticostriatal slice cultures. Furthermore, striatum from corticostriatal cocultures was more sensitive to 3-NPA than...

  1. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux

    2015-07-01

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  2. Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.

    Science.gov (United States)

    Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

    2014-01-01

    "Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.

  3. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  4. Centrality of striatal cholinergic transmission in basal ganglia function

    Directory of Open Access Journals (Sweden)

    Paola eBonsi

    2011-02-01

    Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

  5. Distinctive striatal dopamine signaling after dieting and gastric bypass.

    Science.gov (United States)

    Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

    2015-05-01

    Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  7. Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

    Science.gov (United States)

    Galván, Adriana; McGlennen, Kristine M

    2013-02-01

    Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

  8. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P fetal rat lateral ganglionic...

  9. Control of striatal signaling by G protein regulators

    Directory of Open Access Journals (Sweden)

    Keqiang eXie

    2011-08-01

    Full Text Available Signaling via heterotrimeric G proteins plays a crucial role in modulating the responses of striatal neurons that ultimately shape core behaviors mediated by the basal ganglia circuitry, such as reward valuation, habit formation and movement coordination. Activation of G-protein-coupled receptors (GPCRs by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes and protein kinases. Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling pathways and cellular responses with unique profiles but common molecular mechanisms. Studies over the last decade have revealed that the extent and duration of GPCR signaling are controlled by a conserved protein family named Regulator of G protein Signaling (RGS. RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this review, we discuss the progress made in understanding the roles of RGS proteins in controlling striatal G protein signaling and providing integration and selectivity of signal transmission. We review evidence on the formation of a macromolecular complex between RGS proteins and other components of striatal signaling pathways, their molecular regulatory mechanisms and impacts on GPCR signaling in the striatum obtained from biochemical studies and experiments involving genetic mouse models. Special emphasis is placed on RGS9-2, a member of the RGS family that is highly enriched in the striatum and plays critical roles in drug addiction and motor control.

  10. Motor tics evoked by striatal disinhibition in the rat

    Science.gov (United States)

    Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

    2013-01-01

    Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

  11. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  12. Fast oscillations in cortical-striatal networks switch frequency following rewarding events and stimulant drugs.

    Science.gov (United States)

    Berke, J D

    2009-09-01

    Oscillations may organize communication between components of large-scale brain networks. Although gamma-band oscillations have been repeatedly observed in cortical-basal ganglia circuits, their functional roles are not yet clear. Here I show that, in behaving rats, distinct frequencies of ventral striatal local field potential oscillations show coherence with different cortical inputs. The approximately 50 Hz gamma oscillations that normally predominate in awake ventral striatum are coherent with piriform cortex, whereas approximately 80-100 Hz high-gamma oscillations are coherent with frontal cortex. Within striatum, entrainment to gamma rhythms is selective to fast-spiking interneurons, with distinct fast-spiking interneuron populations entrained to different gamma frequencies. Administration of the psychomotor stimulant amphetamine or the dopamine agonist apomorphine causes a prolonged decrease in approximately 50 Hz power and increase in approximately 80-100 Hz power. The same frequency switch is observed for shorter epochs spontaneously in awake, undrugged animals and is consistently provoked for reward receipt. Individual striatal neurons can participate in these brief high-gamma bursts with, or without, substantial changes in firing rate. Switching between discrete oscillatory states may allow different modes of information processing during decision-making and reinforcement-based learning, and may also be an important systems-level process by which stimulant drugs affect cognition and behavior.

  13. Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

    Science.gov (United States)

    Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

    2014-01-01

    Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

  14. Adrenergic receptor-mediated modulation of striatal firing patterns.

    Science.gov (United States)

    Ohta, Hiroyuki; Kohno, Yu; Arake, Masashi; Tamura, Risa; Yukawa, Suguru; Sato, Yoshiaki; Morimoto, Yuji; Nishida, Yasuhiro; Yawo, Hiromu

    2016-11-01

    Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α 1 -AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α 1 -ARs work in opposition controlling the striatal firing initiation and the firing increment. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  15. The role of striatal NMDA receptors in drug addiction.

    Science.gov (United States)

    Ma, Yao-Ying; Cepeda, Carlos; Cui, Cai-Lian

    2009-01-01

    The past decade has witnessed an impressive accumulation of evidence indicating that the excitatory amino acid glutamate and its receptors, in particular the N-methyl-D-aspartate (NMDA) receptor subtype, play an important role in drug addiction. Various lines of research using animal models of drug addiction have demonstrated that drug-induced craving is accompanied by significant upregulation of NR2B subunit expression. Furthermore, selective blockade of NR2B-containing NMDA receptors in the striatum, especially in the nucleus accumbens (NAc) can inhibit drug craving and reinstatement. The purpose of this review is to examine the role of striatal NMDA receptors in drug addiction. After a brief description of glutamatergic innervation and NMDA receptor subunit distribution in the striatum, we discuss potential mechanisms to explain the role of striatal NMDA receptors in drug addiction by elucidating signaling cascades involved in the regulation of subunit expression and redistribution, phosphorylation of receptor subunits, as well as activation of intracellular signals triggered by drug experience. Understanding the mechanisms regulating striatal NMDA receptor changes in drug addiction will provide more specific and rational targets to counteract the deleterious effects of drug addiction.

  16. In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

    Science.gov (United States)

    Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

    2012-12-16

    Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

  17. Fractal analysis of striatal dopamine re-uptake sites

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

    1997-01-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab

  18. Fractal analysis of striatal dopamine re-uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T.; Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Tiihonen, J.; Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Karhu, J. [Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio (Finland)

    1997-09-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT). The mean fractal dimension was 1.15{+-}0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19{+-}0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab.

  19. Transient and steady-state selection in the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Adam eTomkins

    2014-01-01

    Full Text Available Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role the striatal microcircuit plays in action selection in the basal ganglia-thalamo-cortical loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-thalamo-cortical loop, to asses the computational role the striatum plays in action selection. We identify a robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's Disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. Thus our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients.

  20. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho [University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Seppaenen, Marko [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland); Noponen, Tommi [University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland)

    2014-10-15

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [{sup 123}I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  1. Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence.Methamphetamine users and non-user controls (n = 18 per group completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride.The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008, but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622. The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010, but not methamphetamine users (r = 0.281, p = 0.258, and the group-wise interaction was significant (p = 0.030.These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.

  2. Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion.

    Science.gov (United States)

    Gomide, Vânia C; Chadi, Gerson

    2004-01-01

    Pregnant Wistar rats received a hyperproteic liquid diet containing 37.5% ethanol-derived calories during gestation. Isocaloric amount of liquid diet, with maltose-dextrin substituted for ethanol, was given to control pair-fed dams. Offsprings were allowed to survive until 24 months of age. A set of aged female offsprings of both control diet and ethanol diet groups was registered for spontaneous motor activity, by means of an infrared motion sensor activity monitor, or for apomorphine-induced rotational behavior, while another lot of male offsprings was submitted to an unilateral striatal small mechanical lesion by a needle, 6 days before rotational recordings. Prenatal ethanol did not alter spontaneous motor parameters like resting time as well as the events of small and large movements in the aged offsprings. Bilateral circling behavior was already increased 5 min after apomorphine in the unlesioned offsprings of both the control and ethanol diet groups. However, it lasted more elevated for 45- to 75-min time intervals in the gestational ethanol-exposed offsprings, while decreasing faster in the control offsprings. Apomorphine triggered a strong and sustained elevation of contraversive turns in the striatal-lesioned 24-month-old offsprings of the ethanol group, but only a small and transient elevation was seen in the offsprings of the control diet group. Astroglial and microglial reactions were seen surrounding the striatal needle track lesion. Microdensitometric image analysis demonstrated no differences in the levels of tyrosine hydroxylase immunoreactivity in the striatum of 24-month-old unlesioned and lesioned offsprings of control and alcohol diet groups. The results suggest that ethanol exposure during gestation may alter the sensitivity of dopamine receptor in aged offsprings, which is augmented by even a small striatal lesion.

  3. Revisiting the 'self-medication' hypothesis in light of the new data linking low striatal dopamine to comorbid addictive behavior.

    Science.gov (United States)

    Awad, A George; Voruganti, Lakshmi L N P

    2015-06-01

    Persons with schizophrenia are at a high risk, almost 4.6 times more likely, of having drug abuse problems than persons without psychiatric illness. Among the influential proposals to explain such a high comorbidity rate, the 'self-medication hypothesis' proposed that persons with schizophrenia take to drugs in an effort to cope with the illness and medication side effects. In support of the self-medication hypothesis, data from our earlier clinical study confirmed the strong association between neuroleptic dysphoria and negative subjective responses and comorbid drug abuse. Though dopamine has been consistently suspected as one of the major culprits for the development of neuroleptic dysphoria, it is only recently our neuroimaging studies correlated the emergence of neuroleptic dysphoria to the low level of striatal dopamine functioning. Similarly, more evidence has recently emerged linking low striatal dopamine with the development of vulnerability for drug addictive states in schizophrenia. The convergence of evidence from both the dysphoria and comorbidity research, implicating the role of low striatal dopamine in both conditions, has led us to propose that the person with schizophrenia who develops dysphoria and comorbid addictive disorder is likely to be one and the same.

  4. Increased ventral-striatal activity during monetary decision making is a marker of problem poker gambling severity.

    Science.gov (United States)

    Brevers, Damien; Noël, Xavier; He, Qinghua; Melrose, James A; Bechara, Antoine

    2016-05-01

    The aim of this study was to examine the impact of different neural systems on monetary decision making in frequent poker gamblers, who vary in their degree of problem gambling. Fifteen frequent poker players, ranging from non-problem to high-problem gambling, and 15 non-gambler controls were scanned using functional magnetic resonance imaging (fMRI) while performing the Iowa Gambling Task (IGT). During IGT deck selection, between-group fMRI analyses showed that frequent poker gamblers exhibited higher ventral-striatal but lower dorsolateral prefrontal and orbitofrontal activations as compared with controls. Moreover, using functional connectivity analyses, we observed higher ventral-striatal connectivity in poker players, and in regions involved in attentional/motor control (posterior cingulate), visual (occipital gyrus) and auditory (temporal gyrus) processing. In poker gamblers, scores of problem gambling severity were positively associated with ventral-striatal activations and with the connectivity between the ventral-striatum seed and the occipital fusiform gyrus and the middle temporal gyrus. Present results are consistent with findings from recent brain imaging studies showing that gambling disorder is associated with heightened motivational-reward processes during monetary decision making, which may hamper one's ability to moderate his level of monetary risk taking. © 2015 Society for the Study of Addiction.

  5. Adversity in childhood linked to elevated striatal dopamine function in adulthood

    OpenAIRE

    Egerton, A.; Valmaggia, L. R.; Howes, O. D.; Day, F.; Chaddock, C. A.; Allen, P.; Winton-Brown, T. T.; Bloomfield, M. A. P.; Bhattacharyya, S.; Chilcott, J.; Lappin, J. M.; Murray, R. M.; McGuire, P.

    2016-01-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and he...

  6. Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers.

    Science.gov (United States)

    Oberlin, Brandon G; Albrecht, Daniel S; Herring, Christine M; Walters, James W; Hile, Karen L; Kareken, David A; Yoder, Karmen K

    2015-06-01

    Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood. To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD). NTS subjects (n = 10) and SD (n = 13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND. Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST. Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures.

  7. Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

    Science.gov (United States)

    Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

    2012-08-01

    Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict

  8. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

    2012-07-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

  9. HIV infection results in ventral-striatal reward system hypo-activation during cue processing

    NARCIS (Netherlands)

    Plessis, Stéfan du; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to

  10. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

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    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  11. Correlation between phosphorylation level of a hippocampal 86kDa protein and extinction of a behaviour in a model of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Pires, Rita G W; Pereira, Sílvia R C; Carvalho, Fabiana M; Oliveira-Silva, Ieda F; Ferraz, Vany P; Ribeiro, Angela M

    2007-06-04

    The effects of chronic ethanol and thiamine deficiency, alone or associated, on hippocampal protein phosphorylation profiles ranging in molecular weight from 30 to 250kDa molecular weight, in stimulated (high K(+) concentration) and unstimulated (basal) conditions were investigated. These treatments significantly changed the phosphorylation level of an 86kDa phosphoprotein. Thiamine deficiency, but not chronic ethanol, induced a decrease in a behavioural extinction index, which is significantly correlated to the phosphorylation level of the p86 protein. These data add to and extend previous findings by our laboratory implicating the involvement of hippocampal neurotransmission components in extinction of a behaviour which involves learning of environmental spatial cues.

  12. Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

    Science.gov (United States)

    Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

    2015-01-01

    One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D2/3 receptor binding potential (BPp) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [123I]iodobenzamide ([123I]-IBZM) was used to examine striatal D2/3 receptor BPp. Patients were examined before and after 6 weeks of treatment with the D2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D2/3 receptor BPp at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BPp in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BPp of dopamine D2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BPp have a better treatment response than patients with a high BPp. The results further suggest that functioning may decline at high levels of dopamine receptor blockade. PMID:25698711

  13. Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice.

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    Yukio eYamamura

    2013-02-01

    Full Text Available Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5, which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5 and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15 is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571, a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.

  14. Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

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    Sergi Ferré

    2007-01-01

    Full Text Available By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS. Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit, where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.

  15. Reward inference by primate prefrontal and striatal neurons.

    Science.gov (United States)

    Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

    2014-01-22

    The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

  16. Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

    International Nuclear Information System (INIS)

    Eells, J.T.; Dubocovich, M.L.

    1988-01-01

    The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [ 3 H]dopamine and [ 3 H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [ 3 H]dopamine and [ 3 H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [ 3 H]norepinephrine or [ 3 H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions

  17. Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

    Science.gov (United States)

    Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

    2017-12-13

    A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

  18. Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

    Science.gov (United States)

    Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

    2016-02-01

    Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

  19. Cue-induced striatal dopamine release in Parkinson's disease-associated impulsive-compulsive behaviours.

    Science.gov (United States)

    O'Sullivan, Sean S; Wu, Kit; Politis, Marios; Lawrence, Andrew D; Evans, Andrew H; Bose, Subrata K; Djamshidian, Atbin; Lees, Andrew J; Piccini, Paola

    2011-04-01

    Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive

  20. Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss.

    Science.gov (United States)

    Baldo, Brian A; Hanlon, Erin C; Obermeyer, William; Bremer, Quentin; Paletz, Elliott; Benca, Ruth M

    2013-12-01

    Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

  1. Neurodevelopmental disruption of cortico-striatal function caused by degeneration of habenula neurons.

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    Young-A Lee

    2011-04-01

    Full Text Available The habenula plays an important role on cognitive and affective functions by regulating monoamines transmission such as the dopamine and serotonin, such that its dysfunction is thought to underlie a number of psychiatric conditions. Given that the monoamine systems are highly vulnerable to neurodevelopmental insults, damages in the habenula during early neurodevelopment may cause devastating effects on the wide-spread brain areas targeted by monoamine innervations.Using a battery of behavioral, anatomical, and biochemical assays, we examined the impacts of neonatal damage in the habenula on neurodevelopmental sequelae of the prefrontal cortex (PFC and nucleus accumbens (NAcc and associated behavioral deficits in rodents. Neonatal lesion of the medial and lateral habenula by ibotenic acid produced an assortment of behavioral manifestations consisting of hyper-locomotion, impulsivity, and attention deficit, with hyper-locomotion and impulsivity being observed only in the juvenile period, whereas attention deficit was sustained up until adulthood. Moreover, these behavioral alterations were also improved by amphetamine. Our study further revealed that impulsivity and attention deficit were associated with disruption of PFC volume and dopamine (DA receptor expression, respectively. In contrast, hyper-locomotion was associated with decreased DA transporter expression in the NAcc. We also found that neonatal administration of nicotine into the habenula of neonatal brains produced selective lesion of the medial habenula. Behavioral deficits with neonatal nicotine administration were similar to those caused by ibotenic acid lesion of both medial and lateral habenula during the juvenile period, whereas they were different in adulthood.Because of similarity between behavioral and brain alterations caused by neonatal insults in the habenula and the symptoms and suggested neuropathology in attention deficit/hyperactivity disorder (ADHD, these results

  2. Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

    Science.gov (United States)

    Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

    2015-09-01

    Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically

  3. Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response

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    Hilary M. Dorton

    2018-01-01

    Full Text Available Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1, and peptide YY (PYY, suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen and ventral striatum (nucleus accumbens. The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman’s correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption

  4. Interacção da salinidade e da fertilização azotada na produtividade do milho-grão Relationship between different levels of salinity and nitrogen and maize production

    Directory of Open Access Journals (Sweden)

    M.C. Gonçalves

    2007-01-01

    da salinidade da água de rega, para aplicações de N inferiores a 4.83 g m-2. Este efeito benéfico da salinidade da água de rega, quando ocorre carência de fertilização azotada, pode ser explicado pela substituição, ou troca, no complexo coloidal do solo do ião NH4+, lá existente, pelo ião Na+, da água de rega, ficando o primeiro disponível para a planta. Apresentam-se ainda resultados que mostram as tendências da evolução da salinidade do solo e da produtividade do milho em função dos tratamentos aplicados.Two experimental fields in Herdade da Mitra and Alvalade do Sado, were installed in different soils, using conventional field operations. The crop was Zea Mays irrigated with a triple emitter source irrigation system. In this layout scheme there are 3 sources of water with different water quality: salty water (water source with NaCl dissolved, irrigation water+fertilizer (water source with NH4NO3 added and irrigation water only (fresh water. With the layout it is intended to obtain two gradients: one with different levels of salinity and another with different levels of nitrogen fertilizer, in order to be able to observe the responses of soil and culture to different levels of salinity and fertilizer. The objective of this work is to evaluate if different irrigation water salinity levels can be compensated by nitrogen, and still be able to achieve acceptable crop production levels even with low quality irrigation water. In the process soil solution (EC, soluble cations and nitrates was monitored in the groups, at 20, 40 and 60 cm depth. At the beginning, at the middle and at the end of the irrigation periods, soil samples were also collected at the four Groups and 3 depths (020cm; 20-40cm; 40-60cm to measure soil parameters like the electrical conductivity of the soil saturation extract. Maize harvest was done in a way to evaluate the different production in the various treatments and the paper shows results related with the impact of treatments

  5. O problema da linguagem e o ensino da mecânica quântica no nível médio The language problem in the teaching of quantum mechanics at high school level

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    Iramaia Jorge Cabral de Paulo

    2011-01-01

    Full Text Available Neste artigo, é discutida a questão básica da linguagem e da captação de significados da Mecânica Quântica (MQ como uma questão relevante para a inserção dos seus conceitos fundamentais no Ensino Médio. Sabe-se que a linguagem é fundamental para a compreensão da ciência e a construção de conceitos científicos que, ao mesmo tempo em que são específicos, podem se generalizar no contexto da vida cotidiana. A preocupação com a linguagem configurada e utilizada pela MQ foi evidenciada pelos seus próprios autores. Diante do problema da relação entre a linguagem clássica e a quântica, este trabalho mostra a opção da manutenção da linguagem clássica modificando-se a lógica para tratar os fenômenos quânticos, buscando-se localizar essa opção do ponto de vista epistemológico e suas implicações para o ensino.In this paper the problem of language and the grasping of meanings in quantum mechanics is discussed as a relevant subject for the teaching of basic concepts at high school level. It is well known that language is fundamental for the comprehension of science and for the construction of scientific concepts which are specific but at the same time might be generalized in the context of everyday life. The concern with the language shaped and used by quantum mechanics was externalized by their own creators. Given the problem of the relationship between the classical and the quantum languages, in this paper we argue that a way to deal with quantum phenomena is to keep the classical language but a different logic must be used, and so we are trying to locate this option from an epistemological point of view and show its implications for teaching.

  6. A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.

    Science.gov (United States)

    Rauf, Khalid; Subhan, Fazal; Sewell, Robert D E

    2012-05-01

    Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

    International Nuclear Information System (INIS)

    Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

    1992-01-01

    Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

  8. Plumbemia em trabalhadores da indústria de reciclagem de baterias automotivas da Grande Porto Alegre, RS Blood lead levels in the battery recycling industry of the metropolitan region of Porto Alegre, RS

    Directory of Open Access Journals (Sweden)

    Renato Minozzo

    2008-12-01

    Full Text Available A reciclagem de baterias pode contaminar o ar, o solo e a água, não só no lugar de processamento, mas também nas regiões circunvizinhas, sendo que os resíduos permanecem no local mesmo após o término da atividade. No presente artigo descrevemos os resultados da avaliação da plumbemia em 53 operários que trabalhavam com reciclagem de baterias automotivas e em 53 indivíduos sem história de exposição. Os dados obtidos foram comparados e discutidos em relação às normas do Ministério do Trabalho (MT e da Occupational Safety and Health Administration (OSHA. A plumbemia no sangue do grupo controle foi de 2,44±1,15 µg/dl e, no grupo exposto, de 59,43±28,34 µg/dl, sendo que 79,2% dos indivíduos mostraram níveis acima do valor de referência (até 40 µg/dl. Estudos recentes recomendam estratégias para prevenir a intoxicação com chumbo: identificação, eliminação ou controle da fonte, monitoração da exposição e respectivos danos e um programa de recompra de baterias usadas das por parte da indústria de origem.Battery recycling may contaminate soil, air and water not only at the processing site but also in the neighboring areas, inasmuch as the residues remain at the site even after the end of the activity. In the present article, we describe the results of plumbism evaluation in 53 individuals that work with car battery recycling and 53 individuals without history of lead exposure. The obtained data were compared and discussed according to the regulations of Brazilian Ministry of Labor and OSHA (Occupational Safety and Health Administration. Blood lead levels in the control group were 2.44 ± 1.15 µg/dl and 59.43 ± 28.34 µg/dl in the exposed group. 79.2 % of the individuals presented levels above the reference value (40 µg/dl. Recent studies recommend strategies to prevent lead intoxication: source identification, control or elimination, monitoring of environmental exposure and hazards and a buy-back program of used

  9. Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.

    Science.gov (United States)

    Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre

    2017-12-15

    Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D 1 or D 2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D 2 than on D 1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine

  10. Ventral striatal activity links adversity and reward processing in children.

    Science.gov (United States)

    Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

    2017-08-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Striatal activation reflects urgency in perceptual decision making.

    Science.gov (United States)

    van Maanen, Leendert; Fontanesi, Laura; Hawkins, Guy E; Forstmann, Birte U

    2016-10-01

    Deciding between multiple courses of action often entails an increasing need to do something as time passes - a sense of urgency. This notion of urgency is not incorporated in standard theories of speeded decision making that assume information is accumulated until a critical fixed threshold is reached. Yet, it is hypothesized in novel theoretical models of decision making. In two experiments, we investigated the behavioral and neural evidence for an "urgency signal" in human perceptual decision making. Experiment 1 found that as the duration of the decision making process increased, participants made a choice based on less evidence for the selected option. Experiment 2 replicated this finding, and additionally found that variability in this effect across participants covaried with activation in the striatum. We conclude that individual differences in susceptibility to urgency are reflected by striatal activation. By dynamically updating a response threshold, the striatum is involved in signaling urgency in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Ladinsky, H.

    1986-01-01

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  13. Ventral striatal activity links adversity and reward processing in children

    Directory of Open Access Journals (Sweden)

    Niki H. Kamkar

    2017-08-01

    Full Text Available Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain’s sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

  14. Adenosine A2A receptors and A2A receptor heteromers as key players in striatal function

    Directory of Open Access Journals (Sweden)

    Sergi eFerre

    2011-06-01

    Full Text Available A very significant density of adenosine adenosine A2A receptors (A2ARs is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs. In this localization A2ARs establish reciprocal antagonistic interactions with dopamine D2 receptors (D2Rs. In one type of interaction, A2AR and D2R are forming heteromers and, by means of an allosteric interaction, A2AR counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striato-pallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A2AR agonist and antagonists, respectively. The second type of interaction involves A2AR and D2R that do not form heteromers and takes place at the level of adenylyl-cyclase (AC. Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A2AR from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A2AR-mediated AC activation is unleashed with an increased gene expression and activity of the striato-pallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A2ARs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A2ARs heteromerize with A1 receptors (A1Rs and their activation facilitates glutamate release. These three different types of A2ARs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.

  15. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    Science.gov (United States)

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  16. Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

    Science.gov (United States)

    Morales-Martínez, Adriana; Sánchez-Mendoza, Alicia; Martínez-Lazcano, Juan Carlos; Pineda-Farías, Jorge Baruch; Montes, Sergio; El-Hafidi, Mohammed; Martínez-Gopar, Pablo Eliasib; Tristán-López, Luis; Pérez-Neri, Iván; Zamorano-Carrillo, Absalom; Castro, Nelly; Ríos, Camilo; Pérez-Severiano, Francisca

    2017-09-01

    Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

  17. Serotonin 2A receptor mRNA levels in the neonatal dopamine-depleted rat striatum remain upregulated following suppression of serotonin hyperinnervation.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-08-05

    Sixty days after bilateral dopamine (DA) depletion (>98%) with 6-hydroxydopamine (6-OHDA) in neonatal rats, serotonin (5-HT) content doubled and 5-HT(2A) receptor mRNA expression rose 54% within the rostral striatum. To determine if striatal 5-HT(2A) receptor mRNA upregulation is dependent on increased 5-HT levels following DA depletion, neonatal rats received dual injections of 6-OHDA and 5,7-dihydroxytryptamine (5,7-DHT) which suppressed 5-HT content by approximately 90%. In these 6-OHDA/5,7-DHT-treated rats, striatal 5-HT(2A) receptor mRNA expression was still elevated (87% above vehicle controls). Comparative analysis of 5-HT(2C) receptor mRNA expression yielded no significant changes in any experimental group. These results demonstrate that upregulated 5-HT(2A) receptor biosynthesis in the DA-depleted rat is not dependent on subsequent 5-HT hyperinnervation. Copyright 1999 Elsevier Science B.V.

  18. Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats.

    Science.gov (United States)

    Haider, Saida; Naqvi, Fizza; Batool, Zehra; Tabassum, Saiqa; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

    2012-01-01

    Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one's ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stress, 4h daily for 15 days. Cognitive testing was performed by the Elevated Plus Maze test (EPM) and Novel Object Recognition test (NOR). HPLC-EC was used to determine hippocampal monoamine levels and their metabolites. The data obtained revealed a significant decrease in hippocampal serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) levels, whereas turnover ratios of 5-HT and DA were significantly increased compared to the controls. Rats exposed to noise exhibited a significant decrement in spatial memory. A significantly decreased recognition index of rats exposed to noise as compared to the control was also observed in the NOR test. Results of the present findings suggest the role of decreased hippocampal 5-HT and DA in the impairment of cognitive function following noise exposure.

  19. Effect of in vitro gamma exposure on rat mesencephalic and striatal cellular types and processes length

    International Nuclear Information System (INIS)

    Coffigny, H.; Court, L.

    1994-01-01

    The isolated mesencephalic and striatal cells were irradiated in a dose-range of 0.25 to 3 Gy followed by 3 day of culture. The proportion of monopolar, bipolar, tripolar and multipolar cell population was not obviously modified by irradiation. The processes length was similar to controls, except after 3 Gy exposure, for monopolar and bipolar mesencephalic cells and the tripolar striatal cells where it was increased. In these populations, only cells with long processes seemed to survive. (author)

  20. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

    OpenAIRE

    Herbort, Maike C.; Soch, Joram; W?stenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, J?rgen; Walter, Henrik; Roepke, Stefan; Schott, Bj?rn H.

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BP...

  1. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Science.gov (United States)

    Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

    2010-02-22

    Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  2. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Directory of Open Access Journals (Sweden)

    Alessandro Bertolino

    2010-02-01

    Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  3. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

    OpenAIRE

    Egerton, A.; Howes, O. D.; Houle, S.; McKenzie, K.; Valmaggia, L. R.; Bagby, M. R.; Tseng, H-H; Bloomfield, M. A. P.; Kenk, M.; Bhattacharyya, S.; Suridjan, I.; Chaddock, C. A.; Winton-Brown, T. T.; Allen, P.; Rusjan, P.

    2017-01-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capaci...

  4. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  5. Consumo e digestibilidade de silagens de capim-elefante com diferentes níveis de subproduto da agroindústria da acerola Intake and digestibilit of elefhant grass silages with the diferent levels of acerola industry by-product

    Directory of Open Access Journals (Sweden)

    Ana Cristina Holanda Ferreira

    2010-12-01

    Full Text Available Foi objetivo deste trabalho avaliar o consumo e digestibilidade da MS e nutrientes. de silagens de capim-elefante (CE contendo subproduto do processamento da acerola desidratada (SACD. Utilizaram-se 20 ovinos machos nãocastrados, distribuídos em delineamento inteiramente casualizado, com cinco níveis de SACD na silagem (0; 3,5; 7; 10,5 e 14% da matéria seca e quatro repetições. Estimaram-se os consumos de matéria seca (MS, celulose, hemicelulose, proteína bruta (PB, fibra em detergente neutro (FDN, fibra em detergente ácido (FDA, bem como os consumos de matéria seca (MSD, proteína bruta (PBD, fibra em detergente neutro (FDND e energia digestível (ED. Foram avaliados também as digestibilidades da MS, PB, FDN, FDA, celulose, hemicelulose e EB, e o balanço de nitrogênio (BN. A adição de SACD, não influenciou o consumo de MS, FDN e FDA em g animal-1 dia-1 e g UTM-1 (unidade de tamanho metabólico = PV0,75, MSD, FDND em g animal-1 dia-1 e ED (0,86 Mcal dia-1. Contudo, a adição de 1% do SACD na ensilagem do capim-elefante resultou em aumento de 1,91 e 0,04 g nos consumos diários de PB e PBD, respectivamente. Com a adição do SACD, não houve alterações na digestibilidade da MS (43%, PB (36,4%, FDN (44,8% e BN (0,22 g dia-1 das silagens. Entretanto, o BN atingiu valores positivos quando foram adicionados 10,5 e 14% do SACD à dieta. O subproduto da acerola desidratado pode ser adicionado em níveis de até 14% da matéria natural na ensilagem de capim-elefante, pois não compromete nem o consumo nem a digestibilidade dos nutrientes em ovinos.The present study aimed to determine de nutritional value of mixed elephant grass silages and increasing levels of dehydrated acerola industry by-product (PAC. Five PAC levels (0; 3.5; 7.0; 10.5 and 14% were evaluated in a digestibility trial with 20 male non-castrated sheep in a randomized experimental design of five treatments (PAC levels and four replications per treatment (sheep. Intake

  6. Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: Implications for anhedonia, anxiety and treatment response.

    Science.gov (United States)

    Peciña, Marta; Sikora, Magdalena; Avery, Erich T; Heffernan, Joseph; Peciña, Susana; Mickey, Brian J; Zubieta, Jon-Kar

    2017-10-01

    Dopamine (DA) neurotransmission within the brain's reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D 2/3 receptor-selective radiotracer [ 11 C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC). We investigated the relationship between D 2/3 receptor availability and baseline measures of depression severity, anxiety, anhedonia, and cognitive and pharmacological mechanisms of treatment response. We found that, compared to controls, patients with depression showed greater D 2/3 receptor availability in several striatal regions, including the bilateral ventral pallidum/nucleus accumbens (vPAL/NAc), and the right ventral caudate and putamen. In the depressed sample, D 2/3 receptor availability in the caudal portion of the ventral striatum (NAc/vPAL) correlated with higher anxiety symptoms, whereas D 2/3 receptor availability in the rostral area of the ventral striatum correlated negatively with the severity of motivational anhedonia. Finally, MDD non-remitters showed greater baseline anxiety, greater D 2/3 availability in the NAc/vPAL, and greater placebo-induced DA release in the bilateral NAc. Our results demonstrate abnormally high D 2/3 receptor availability in the ventral striatum of patients with MDD, which seem to be associated with comorbid anxiety symptoms and lack of response to antidepressants. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  7. Effects of hypoxic–ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoyu; Cao Li; Guo Qiyong; Wang Xiaoming

    2011-01-01

    Introduction: Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic–ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ( 11 C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using 11 C-CFT PET. Methods: Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with 11 C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure. Results: A few minutes after intravenous injection of 11 C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P 11 C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P 11 C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.

  8. Characterization of the effects of serotonin on the release of [3H]dopamine from rat nucleus accumbens and striatal slices

    International Nuclear Information System (INIS)

    Nurse, B.; Russell, V.A.; Taljaard, J.J.

    1988-01-01

    The effect of serotonin agonists on the depolarization (K+)-induced, calcium-dependent, release of [ 3 H]dopamine (DA) from rat nucleus accumbens and striatal slices was investigated. Serotonin enhanced basal 3 H overflow and reduced K+-induced release of [ 3 H]DA from nucleus accumbens slices. The effect of serotonin on basal 3 H overflow was not altered by the serotonin antagonist, methysergide, or the serotonin re-uptake blocker, chlorimipramine, but was reversed by the DA re-uptake carrier inhibitors nomifensine and benztropine. With the effect on basal overflow blocked, serotonin did not modulate K+-induced release of [ 3 H]DA in the nucleus accumbens or striatum. The serotonin agonists, quipazine (in the presence of nomifensine) and 5-methoxytryptamine, did not significantly affect K+-induced release of [ 3 H]DA in the nucleus accumbens. This study does not support suggestions that serotonin receptors inhibit the depolarization-induced release of dopamine in the nucleus accumbens or striatum of the rat brain. The present results do not preclude the possibility that serotonin may affect the mesolimbic reward system at a site which is post-synaptic to dopaminergic terminals in the nucleus accumbens

  9. History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine.

    Science.gov (United States)

    Oswald, Lynn M; Wand, Gary S; Kuwabara, Hiroto; Wong, Dean F; Zhu, Shijun; Brasic, James R

    2014-06-01

    Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, aged 18-29 years, underwent two consecutive 90-min positron emission tomography studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

  10. Striatal [[sup 11]C]-N-methyl-spiperone binding in patients with focal dystonia (torticollis) using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Leenders, K [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Hartvig, P [Hospital Pharmacy, Univ. Hospital, Uppsala (Sweden); Forsgren, L; Holmgren, G; Almay, B [Dept. of Neurology, Umeaa Univ., Umeaa (Sweden); Eckernaes, S A [Dept. of Neurology, Univ. Hospital, Uppsala (Sweden); Lundqvist, H; Laangstroem, B [Uppsala Univ. PET-Center, Uppsala (Sweden)

    1993-01-01

    Specific binding of [[sup 11]C]-N-methyl-spiperone to striatal dopamine D2 receptors was assessed using positron emission tomography (PET) in 6 patients with adult-onset focal dystonia (predominantly spasmodic torticollis) and in 5 healthy subjects. No significant difference in average specific striatal tracer uptake between patients and healthy subjects was found. However, in the 5 patients showing lateralisation of clinical signs a trend to higher striatal tracer uptake in the contralateral hemisphere was observed. (authors).

  11. Evaluation of testosterone serum levels in testicular interstitial fluid under thyroxine influence; Avaliacao da testosterona no fluido intersticial testicular sob influencia da tiroxina

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Isvania Maria S. da; Pereira, Simey de L.S.; Souza, Grace Mary L.; Carvalho, Elaine F.M.B.; Catanho, Maria Teresa J. de A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Silveira, Maria de Fatima G. da [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia; Lima Filho, Guilherme L. [Universidade de Pernambuco (UPE), Nazare da Mata, PE (Brazil). Faculdade de Formacao de Professores

    2000-07-01

    The thyroid hormones possibly exert a reciprocal action between testicular steroids and Sertoli's cells during the premature period. This work aims to evaluate thyroxine effect on testosterone serum levels and in the testicular interstitial fluid (TIF) in rats. Wistar males rats, 22 days old, 80g of body weight, were induced to hyperthyroidism with thyroxine (20{mu}g/kg) in periods of 5, 10, 15 and 20 consecutive days. After the treatment the animals were weighed and sacrificed for blood and testis collection. From the blood serum and from the TIF drained from the testis were performed testes in order to obtain testosterone attached to {sup 125} I with a specific activity of 36,86 MBq/ig. The results have shown a testosterone significant lineal increase in both - serum and TIF - in the group treated with thyroxine as a time function. In the control group, testosterone levels remained low in both serum and TIF dosages. As a result, we were able to verify that the testosterone levels could be modified by thyroxine in serum and TIF. And so, it could affect luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in hypophysis. (author)

  12. Effect of genotype and dietary protein level on lamb meat quality Efeito do genótipo e do teor de proteína da dieta sobre a qualidade da carne de cordeiros

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    Tânia Mara Azevedo de Lima

    2011-09-01

    Full Text Available This study aimed to evaluate the lamb meat quality of Santa Ines and Dorper x Santa Ines lambs fed 12 or 20% dietary crude protein (CP level. Twenty four animals were used, with initial weight of 17 ± 1,82kg, individually penned, fed 40% of corn silage and 60% of concentrate and slaughtered at 35 kg of body weight. After carcass cooling, a sample of Longissimus dorsi was removed to determine the chemical composition and the meat quality characteristics. There was no effect for moisture (71,74%, protein (21,43% and minerals (1,08%, however, Santa Ines lambs showed higher fat content in meat in relation to cross Dorper x Santa Ines when fed 20% of CP (4,43%. The genotype and crude protein level of diet did not affect pH (5,65, cholesterol (28,28mg/100g of meat, water activity (1,002, color (L*: 41,20; a*: 15,62; b*: 5,09, cooking weight loss (35,98%, shear force (1,10kgf/cm2 and water holding capacity of meat (60,18%. The meat of crossbred lambs Dorper x Santa Ines showed less fat when fed 12 and 20% of dietary crude protein and could constitute a marketing tool to promote the meat from this cross. Protein levels evaluated did not affect the quality characteristics of lamb meat, being able to use the lowest level (12%, aiming the formulation of economic diets for producer, since that it also allows satisfactory animal performance.O objetivo com este trabalho foi avaliar a qualidade da carne de cordeiros Santa Inês e Dorper x Santa Inês, alimentados com 12 ou 20% de proteína bruta (PB na dieta. Foram utilizados 24 animais, com peso corporal inicial de 17 ± 1,82kg, confinados individualmente, alimentados com 40% de silagem de milho e 60% de concentrado, abatidos aos 35kg de peso corporal. Após o resfriamento das carcaças, retirou-se uma amostra do músculo Longissimus dorsi para determinação da composição química e das características qualitativas da carne. Não houve efeito para umidade (71,74%, proteína (21,43% e minerais (1

  13. β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

    Science.gov (United States)

    Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

    2010-01-01

    Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

  14. Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

    Science.gov (United States)

    Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

    2018-01-01

    Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

  15. Lower glutamic acid decarboxylase 65-kDa isoform messenger RNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia.

    Science.gov (United States)

    Glausier, Jill R; Kimoto, Sohei; Fish, Kenneth N; Lewis, David A

    2015-01-15

    Altered gamma-aminobutyric acid (GABA) signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in patients with schizophrenia and schizoaffective disorder. Levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67-kDa isoform (GAD67) in the PFC have been consistently reported to be lower in patients with these disorders, but the status of the second GABA-synthesizing enzyme, glutamic acid decarboxylase 65-kDa isoform (GAD65), remains unclear. GAD65 messenger RNA (mRNA) levels were quantified in PFC area 9 by quantitative polymerase chain reaction from 62 subjects with schizophrenia or schizoaffective disorder and 62 matched healthy comparison subjects. In a subset of subject pairs, GAD65 relative protein levels were quantified by confocal immunofluorescence microscopy. Mean GAD65 mRNA levels were 13.6% lower in subjects with schizoaffective disorder but did not differ in subjects with schizophrenia relative to their matched healthy comparison subjects. In the subjects with schizoaffective disorder, mean GAD65 protein levels were 19.4% lower and were correlated with GAD65 mRNA levels. Lower GAD65 mRNA and protein levels within subjects with schizoaffective disorder were not attributable to factors commonly comorbid with the diagnosis. In concert with previous studies, these findings suggest that schizoaffective disorder is associated with lower levels of both GAD65 and GAD67 mRNA and protein in the PFC, whereas subjects with schizophrenia have lower mean levels of only GAD67 mRNA and protein. Because cognitive function is generally better preserved in patients with schizoaffective disorder relative to patients with schizophrenia, these findings may support an interpretation that GAD65 downregulation provides a homeostatic response complementary to GAD67 downregulation that serves to reduce inhibition in the face of lower PFC network activity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc

  16. The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

    Directory of Open Access Journals (Sweden)

    Twum eAnsah

    2011-06-01

    Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

  17. Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games.

    Science.gov (United States)

    Set, Eric; Saez, Ignacio; Zhu, Lusha; Houser, Daniel E; Myung, Noah; Zhong, Songfa; Ebstein, Richard P; Chew, Soo Hong; Hsu, Ming

    2014-07-01

    Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance--catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase--modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function--dopamine transporter and D2 receptors--was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.

  18. Differential coding of reward and movement information in the dorsomedial striatal direct and indirect pathways.

    Science.gov (United States)

    Shin, Jung Hwan; Kim, Dohoung; Jung, Min Whan

    2018-01-26

    The direct and indirect pathways of the basal ganglia have long been thought to mediate behavioral promotion and inhibition, respectively. However, this classic dichotomous model has been recently challenged. To better understand neural processes underlying reward-based learning and movement control, we recorded from direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in the dorsomedial striatum of D1-Cre and D2-Cre mice performing a probabilistic Pavlovian conditioning task. dSPNs tend to increase activity while iSPNs decrease activity as a function of reward value, suggesting the striatum represents value in the relative activity levels of dSPNs versus iSPNs. Lick offset-related activity increase is largely dSPN selective, suggesting dSPN involvement in suppressing ongoing licking behavior. Rapid responses to negative outcome and previous reward-related responses are more frequent among iSPNs than dSPNs, suggesting stronger contributions of iSPNs to outcome-dependent behavioral adjustment. These findings provide new insights into striatal neural circuit operations.

  19. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Science.gov (United States)

    Warren, Emily Booth; Aicher, Aidan Edward; Fessel, Joshua Patrick; Konradi, Christine

    2017-01-01

    Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  20. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Directory of Open Access Journals (Sweden)

    Emily Booth Warren

    Full Text Available Mitochondrial DNA (mtDNA, the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD patients who had developed L-DOPA Induced Dyskinesia (LID, compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  1. Hypercholesterolemia causes psychomotor abnormalities in mice and alterations in cortico-striatal biogenic amine neurotransmitters: Relevance to Parkinson's disease.

    Science.gov (United States)

    Paul, Rajib; Choudhury, Amarendranath; Chandra Boruah, Dulal; Devi, Rajlakshmi; Bhattacharya, Pallab; Choudhury, Manabendra Dutta; Borah, Anupom

    2017-09-01

    The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. However, the role of hypercholesterolemia on brain functions in terms of neurotransmitter metabolism and associated behavioral manifestations remain elusive. We tested in Swiss albino mice whether hypercholesterolemia induced by high-cholesterol diet would affect dopamine and serotonin metabolism in discrete brain regions that would precipitate in psychomotor behavioral manifestations. High-cholesterol diet for 12 weeks caused a significant increase in blood total cholesterol level, which validated the model as hypercholesterolemic. Tests for akinesia, catalepsy, swimming ability and gait pattern (increased stride length) have revealed that hypercholesterolemic mice develop motor behavioral abnormalities, which are similar to the behavioral phenotypes of PD. Moreover, hypercholesterolemia caused depressive-like behavior in mice, as indicated by the increased immobility time in the forced swim test. We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

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    Jae Jung Lee

    2015-09-01

    Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

  3. Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

    Science.gov (United States)

    Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

    1998-08-01

    The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

  4. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

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    Youngbin Kwak

    2010-09-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

  5. An inquiry into the semiquantitative parameters of striatal dopamine receptor imaging

    International Nuclear Information System (INIS)

    Cao Guoxiang; Tan Tianzhi; Kuang Anren; Liang Zhenglu

    1998-01-01

    Purpose: To inquire into the optimal striatal reference region for nonspecific IBZM uptake in brain dopamine receptor imaging. Methods: Using in vivo data from rats, the authors compared the results of 125 I-iodobenzamide ( 125 I-IBZM) striatal specific binding that were respectively obtained taking cerebellum and frontal cortex as striatal reference region of nonspecific uptake of ligand. Results: Radioiodination labelled IBZM bound stereoselectively and reversibly to striatal D2 receptors. Frontal cortex and cerebellum showed rapid uptake and rapid washout of ligand. When cerebellar uptake was used as a reference of nonspecific uptake in striatum, IBZM saturation could not be demonstrated. But when the frontal cortex was used as reference region, saturation could be demonstrated with B max = 44 pmol/g striatum tissue. The percentage of haloperidol replacement and the percentage of uptake difference between striatum and other brain regions which were derived from competitive inhibition experiments with a large does of spiperone or haloperidol, suggested that the cerebellar uptake underestimated nonspecific uptake in the striatum while frontal cortex was an appropriate reference region for nonspecific uptake of ligand in striatum. Conclusions: For the calculation of specific IBZM binding and other semiquantitative parameters of striatal dopamine D2 receptor imaging, frontal cortex would be the nonspecific reference region of choice

  6. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Elevated Striatal Reactivity Across Monetary and Social Rewards in Bipolar I Disorder

    Science.gov (United States)

    Dutra, Sunny J.; Cunningham, William A.; Kober, Hedy; Gruber, June

    2016-01-01

    Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation employed both a monetary and social incentive delay task among adults with remitted BD type I (N=24) and a healthy non-psychiatric control group (HC; N=25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated ventral and dorsal striatal reactivity across monetary and social reward receipt, but not anticipation, in the BD group. Post-hoc analyses further suggested that greater striatal reactivity to reward receipt across monetary and social reward tasks predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC, but not BD, group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of reward reactivity. PMID:26390194

  8. Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

    International Nuclear Information System (INIS)

    Cherubini, Marta; Ginés, Silvia

    2017-01-01

    Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

  9. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

  10. Impacto da Pastoral da Criança sobre a nutrição de menores de cinco anos no Maranhão: uma análise multinível Impact of Pastoral da Criança on the nutrition of children under 5 years of age in Maranhão: a multi-level analysis

    Directory of Open Access Journals (Sweden)

    Nelson A. Neumann

    2002-04-01

    ,63 respectivamente, ambas com pBACKGOUND: Pastoral da Criança monitors more than 1.5 million children monthly in the promotion of mother-child health. Independent assessments are necessary in order to evaluate its impact. OBJECTIVE: To compare child nutrition indicators in communities served by Pastoral da Criança and in control communities through traditional and multi-level analysis. OUTLINE: Quasi-experimental study, comparing conglomerates of children monitored by 60 community leaders of Pastoral and control conglomerates. SITE: Urban and rural areas (cities of São Luís and Timbiras in Maranhão. PARTICIPANTS: 60 conglomerates in each group (Pastoral and Control and an average of 14 children per conglomerate. The study effectively included 1,629 children, of whom 820 were monitored by Pastoral. RESULTS: Result analysis was conducted by using traditional methods, which do not consider data hierarchy structure, and by considering intra-group correlations by means of multi-level analysis. The latter showed that the regression model variability was distributed along all 4 levels studied. In the traditional analysis of the height-for-age Z-score, Pastoral children were, on average, 0.184 Z-score shorter than control children (P=0.03. After adjustment for the confounding factors score, this difference increased. However, the effect decreased when adjusted for children's ages and was no longer significant. The multi-level analysis did not reveal a significant effect of Pastoral on any of the adjustment models, differently from the traditional analysis. Both traditional and multi-level analyses were similar as to the results of exclusive or predominant breastfeeding up to the third month of life, both showing a positive Pastoral da Criança influence, both in the general and adjusted analyses (odd ratios of 4.37 and 4.63 respectively, both with p<0.001. CONCLUSION: The assessment showed that, by not considering intra-class correlations, traditional analysis may present different

  11. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.

    Science.gov (United States)

    Kaasinen, Valtteri; Vahlberg, Tero

    2017-12-01

    A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882. © 2017 American Neurological Association.

  12. Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

    Science.gov (United States)

    Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

    2016-01-01

    Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

  13. Uso combinado da laserterapia de baixa potência e da inibição da ciclooxigenase-2 na reepitelização de ferida incisional em pele de camundongos: um estudo pré-clínico Combined use of low level laser therapy and cyclooxygenase-2 selective inhibition on skin incisional wound reepithelialization in mice: a preclinical study

    Directory of Open Access Journals (Sweden)

    Cíntia Helena Santuzzi

    2011-04-01

    Full Text Available FUNDAMENTOS: A laserterapia de baixa potência e os inibidores seletivos da ciclooxigenase-2 (ICOX2 vem sendo muito utilizados para modular a resposta inflamatória, entretanto, os seus efeitos na reepitelização de feridas não são bem compreendidos. OBJETIVO: Avaliar os efeitos isolados e combinados da laserterapia de baixa potência e da ICOX2 na reepitelização de ferida incisional na pele de camundongos. MÉTODO: Foi induzida uma ferida de 1 cm no dorso de cada camundongo, que foram divididos em quatro grupos (N=20: Controle, Laserterapia, Tratados com celecoxib e Terapia conjugada. Os animais dos grupos celecoxib e Terapia conjugada foram tratados com celecoxib por 10 dias antes da incisão cutânea. As feridas experimentais foram irradiadas com laserterapia de baixa potência He-Ne (632nm, dose: 4J/cm2 em varredura, por 12 segundos durante três dias consecutivos nos grupos Laserterapia e Terapia conjugada. Os animais foram sacrificados no 3º dia de pós-operatório. Amostras das feridas foram coletadas e coradas (Tricromio de Masson para análise histomorfométrica. RESULTADOS: Tanto o grupo Laserterapia, quanto o grupo celecoxib, mostrou aumento da reepitelização cutânea em relação ao grupo Controle, entretanto, o grupo Terapia conjugada não apresentou diferenças. Quanto à queratinização o grupo Laserterapia e Terapia conjugada apresentaram redução dos queratinócitos, comparados com o grupo Controle. CONCLUSÕES: Os resultados mostram que o uso da laserterapia de baixa potência e da ICOX2 isoladamente aumentam as células epiteliais, mas somente a laserterapia de baixa potência reduziu os queratinócitos cutâneos. O tratamento conjugado restabelece a reepitelização inata e dimunui a queratinização, embora ocorra uma acelerada contração da ferida com melhora na organização da ferida na pele de camundongos.BACKGROUND: Low level laser therapy and cyclooxygenase-2 (ICOX2 selective inhibitors have been widely used

  14. Learning new sequential stepping patterns requires striatal plasticity during the earliest phase of acquisition.

    Science.gov (United States)

    Nakamura, Toru; Nagata, Masatoshi; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo; Kitsukawa, Takashi

    2017-04-01

    Animals including humans execute motor behavior to reach their goals. For this purpose, they must choose correct strategies according to environmental conditions and shape many parameters of their movements, including their serial order and timing. To investigate the neurobiology underlying such skills, we used a multi-sensor equipped, motor-driven running wheel with adjustable sequences of foothold pegs on which mice ran to obtain water reward. When the peg patterns changed from a familiar pattern to a new pattern, the mice had to learn and implement new locomotor strategies in order to receive reward. We found that the accuracy of stepping and the achievement of water reward improved with the new learning after changes in the peg-pattern, and c-Fos expression levels assayed after the first post-switch session were high in both dorsolateral striatum and motor cortex, relative to post-switch plateau levels. Combined in situ hybridization and immunohistochemistry of striatal sections demonstrated that both enkephalin-positive (indirect pathway) neurons and substance P-positive (direct pathway) neurons were recruited specifically after the pattern switches, as were interneurons expressing neuronal nitric oxide synthase. When we blocked N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum by injecting the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), we found delays in early post-switch improvement in performance. These findings suggest that the dorsolateral striatum is activated on detecting shifts in environment to adapt motor behavior to the new context via NMDA-dependent plasticity, and that this plasticity may underlie forming and breaking skills and habits as well as to behavioral difficulties in clinical disorders. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Potencial produtivo, alterações da estrutura e qualidade da pastagem de milheto submetida a diferentes níveis de nitrogênio Productive potential, structure changes and quality of pearl millet under different nitrogen levels

    Directory of Open Access Journals (Sweden)

    Ingrid Heringer

    2002-04-01

    Full Text Available Com o objetivo de estudar a produção de matéria seca (MS, eficiência de utilização, taxa de recuperação do N, densidade e qualidade de forragem, foi realizado um experimento de pastejo em milheto sob níveis crescentes de N (0, 150, 300, 450 e 600 kg/ha, em um delineamento completamente casualizado com duas repetições. Foram estudadas a densidade de forragem por estrato e total e a distribuição dos componentes lâmina foliar, colmo + bainha e material morto nos distintos estratos da pastagem (0-10, 10-20, 20-30, 30-40 e >40 cm acima do nível do solo. Utilizaram-se novilhas em um sistema de pastejo contínuo com uma oferta de 10 kg/dia de MS/100 kg PV. Para manter a oferta pretendida, foi usada a técnica "put-and-take". A produção de MS apresentou relação quadrática com os níveis de N. A taxa de recuperação e de eficiência de utilização do N mostraram relação linear negativa com as doses de N. Houve aumento na contribuição de lâminas foliares e redução no percentual de colmos + bainhas, material morto e na densidade da forragem do estrato inferior até o topo da pastagem em todos tratamentos. A adubação nitrogenada não alterou a densidade de forragem e a relação folha/colmo. A relação dos níveis de N com a porcentagem de proteína bruta das frações colmo + bainha e material morto, foi linear positiva do topo para a base da pastagem e para lâminas foliares até 30 cm de altura. A digestibilidade in vitro da matéria orgânica dos componentes foi indiferente aos níveis de N, à exceção de lâminas foliares acima de 10 cm, que apresentaram relação quadrática com as doses de N.It was conducted an experiment with pearl millet under grazing with different levels of N (0, 250, 300, 450 and 600 kg/ha. The objective was to study the dry matter (DM production, the utilization efficiency, the recuperation rate, forage density and quality. The experiment was completely randomized design with two replications

  16. Os níveis de desenvolvimento socioeconômico da população da Amazônia brasileira: 1970 e 1980 Levels of socioeconomic development in the Brazilian Amazon: 1970 and 1980

    Directory of Open Access Journals (Sweden)

    Archibald O. Haller

    2000-09-01

    Full Text Available O artigo discute uma tipologia das áreas de fronteira na Amazônia brasileira e a relevância do conceito de fronteira para o estudo da emergência de anomia social nessas áreas. Propõe correlação positiva entre mudança social acelerada e fatos sociais anômicos, diluição de famílias, criminalidade, violência etc. Apresenta escores dos níveis de desenvolvimento socioeconômico per capita (DSE/kmu das populações de todos os municípios da Amazônia Legal para 1970 e 1980, e conclui que os escores de 327 dos 329 municípios estudados cresceram, o que indica a melhora das condições de vida da população regional, contradizendo a hipótese, comum na literatura, de disrupção social na Amazônia brasileira. Assim, a anomia deve ser esperada com a mudança acelerada. Fatos anômicos não desmentem as melhoras socioeconômicas.The text presents a typology of the different frontier areas within the Brazilian Amazon today and discusses the relevance of the concept of frontier in studying the emergence of social anomie in those areas. It suggests there is a positive correlation between the processes of accelerated social change characteristic of such areas and signs of social anomie, such as the loosening of family and personal ties, increased crime and violence, deterioration of the public order, etc. Per capita levels of socioeconomic development (DSE/kmu were measured among people residing in all municipalities within the administrative region known as Amazônia Legal, for 1970 and 1980. Growth in the scores of 327 of the 329 municipalities under study indicates a strong trend towards improvement of living conditions for the region’s residents. This contradicts the hypothesis found in most of the analytical literature, which contends that the Brazilian Amazon has been stage to social disruption or stagnation. The text argues that anomie is to be expected in situations of accelerated social change, where people, values, and identities

  17. Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms.

    Science.gov (United States)

    Radl, Daniela; Chiacchiaretta, Martina; Lewis, Robert G; Brami-Cherrier, Karen; Arcuri, Ludovico; Borrelli, Emiliana

    2018-01-02

    The dopamine D2 receptor (D2R) is a major component of the dopamine system. D2R-mediated signaling in dopamine neurons is involved in the presynaptic regulation of dopamine levels. Postsynaptically, i.e., in striatal neurons, D2R signaling controls complex functions such as motor activity through regulation of cell firing and heterologous neurotransmitter release. The presence of two isoforms, D2L and D2S, which are generated by a mechanism of alternative splicing of the Drd2 gene, raises the question of whether both isoforms may equally control presynaptic and postsynaptic events. Here, we addressed this question by comparing behavioral and cellular responses of mice with the selective ablation of either D2L or D2S isoform. We establish that the presence of either D2L or D2S can support postsynaptic functions related to the control of motor activity in basal conditions. On the contrary, absence of D2S but not D2L prevents the inhibition of tyrosine hydroxylase phosphorylation and, thereby, of dopamine synthesis, supporting a major presynaptic role for D2S. Interestingly, boosting dopamine signaling in the striatum by acute cocaine administration reveals that absence of D2L, but not of D2S, strongly impairs the motor and cellular response to the drug, in a manner similar to the ablation of both isoforms. These results suggest that when the dopamine system is challenged, D2L signaling is required for the control of striatal circuits regulating motor activity. Thus, our findings show that D2L and D2S share similar functions in basal conditions but not in response to stimulation of the dopamine system.

  18. Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Scallet, A.C.; Holson, R.R.; Lipe, G.W.; Slikker, W. Jr.; Ali, S.F.

    1991-01-01

    The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [ 3 H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg 2+ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [ 3 H]dopamine and [ 3 H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg 2+ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg 2+ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg 2+ present, 1 mM glutamine increased glutamate release and induced the release of [ 3 H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%

  19. Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors' in Mice

    Science.gov (United States)

    Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

    2016-01-01

    Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia. PMID:26228524

  20. Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at-risk youth.

    Science.gov (United States)

    Weiland, Barbara J; Zucker, Robert A; Zubieta, Jon-Kar; Heitzeg, Mary M

    2017-03-01

    Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamine-induced dopamine release, in substance users compared with healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However, other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multi-modal molecular and neural imaging of the dopaminergic system. Forty-four young adult male subjects performed monetary incentive delay tasks during both [ 11 C]raclopride positron emission tomography and functional magnetic resonance imaging scans. FH+ subjects were identified as low (n = 24) or high risk (n = 9) based on early initiation of drunkenness. FH+ high-risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ low risk subjects and controls with no familial loading (n = 11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in at-risk individuals, higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype. © 2016 Society for the Study of Addiction.

  1. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

    NARCIS (Netherlands)

    Mencacci, N.E.; Kamsteeg, E.J.; Nakashima, K.; R'Bibo, L.; Lynch, D.S.; Balint, B.; Willemsen, M.A.A.P.; Adams, M.E.; Wiethoff, S.; Suzuki, K.; Davies, C.H.; Ng, J.; Meyer, E.; Veneziano, L.; Giunti, P.; Hughes, D.; Raymond, F.L.; Carecchio, M.; Zorzi, G.; Nardocci, N.; Barzaghi, C.; Garavaglia, B.; Salpietro, V.; Hardy, J.; Pittman, A.M.; Houlden, H.; Kurian, M.A.; Kimura, H.; Vissers, L.E.L.M.; Wood, N.W.; Bhatia, K.P.

    2016-01-01

    Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very

  2. Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

    2005-01-01

    Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

  3. Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

    Science.gov (United States)

    Cyr, Marilyn; Yang, Xiao; Horga, Guillermo; Marsh, Rachel

    2018-04-01

    This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions. © 2018 Wiley Periodicals, Inc.

  4. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    International Nuclear Information System (INIS)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W.

    1992-01-01

    An 123 I labeled cocaine analog, 4'-[ 123 I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author)

  5. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  6. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jilly Naaijen

    2017-01-01

    Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

  7. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Forde, Natalie J.; Lythgoe, David J.; Akkermans, Sophie E. A.; Openneer, Thaira J. C.; Dietrich, Andrea; Zwiers, Marcel P.; Hoekstra, Pieter J.; Buitelaar, Jan K.

    2017-01-01

    Objective: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently

  8. Adversity in childhood linked to elevated striatal dopamine function in adulthood.

    Science.gov (United States)

    Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

    2016-10-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

    DEFF Research Database (Denmark)

    Ziebell, Morten; Andersen, Birgitte B; Pinborg, Lars H

    2013-01-01

    cognitively evaluated with the Mini Mental State Examination. RESULTS: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. CONCLUSION: In patients with newly diagnosed DLB...

  10. Indicadores socioambientais para vigilância da dengue em nível local Socio-environmental indicators for dengue surveillance in the local level

    Directory of Open Access Journals (Sweden)

    Regina Fernandes Flauzino

    2011-03-01

    Full Text Available Este artigo caracteriza uma localidade quanto às condições de saneamento e processos de degradação ambiental que possam estar relacionados à transmissão da dengue, além de discutir a construção de novos indicadores socioambientais visando à vigilância epidemiológica. A área de estudo foi a Ilha da Conceição, no município de Niterói, RJ. Informantes-chave foram entrevistados para obter informações que pudessem ser utilizadas nas construções de novos indicadores. Ao se compararem os dados do IBGE com os fornecidos pelos informantes, foram encontradas algumas diferenças. Os dados dos informantes são mais condizentes com a realidade local, propiciando, de acordo com a área, a observação de diferentes modus operandi de coleta de lixo e limpeza pública. Os casos concentraram-se nos setores favela plana e favela morro. Concluiu-se que os indicadores referentes à frequência de abastecimento de água e coleta de lixo se mostram importantes para serem analisados em estudos de nível local associados com a incidência da dengue.This paper characterizes a local area in terms of sanitary conditions and environmental degradation processes that may be related to dengue transmission, and discusses the construction of new social and environmental indicators aiming at epidemiological surveillance. The studied area was Ilha da Conceição, in the municipality of Niterói, state of Rio de Janeiro. Key informants were interviewed to obtain information that could be used in the construction of new indicators. Comparing the data from the IBGE with those provided by the informants, we found some differences. The data provided by the latter are more reliable regarding the local reality, and they enable, according to the area, the observation of different modus operandi of garbage collection and public cleansing. The cases were concentrated on flat slum and hill slum areas. It was concluded that it is important to analyze indicators

  11. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model.

    Science.gov (United States)

    Wu, Jun; Ryskamp, Daniel A; Liang, Xia; Egorova, Polina; Zakharova, Olga; Hung, Gene; Bezprozvanny, Ilya

    2016-01-06

    In Huntington's disease (HD), mutant Huntingtin (mHtt) protein causes striatal neuron dysfunction, synaptic loss, and eventual neurodegeneration. To understand the mechanisms responsible for synaptic loss in HD, we developed a corticostriatal coculture model that features age-dependent dendritic spine loss in striatal medium spiny neurons (MSNs) from YAC128 transgenic HD mice. Age-dependent spine loss was also observed in vivo in YAC128 MSNs. To understand the causes of spine loss in YAC128 MSNs, we performed a series of mechanistic studies. We previously discovered that mHtt protein binds to type 1 inositol (1,4,5)-trisphosphate receptor (InsP3R1) and increases its sensitivity to activation by InsP3. We now report that the resulting increase in steady-state InsP3R1 activity reduces endoplasmic reticulum (ER) Ca(2+) levels. Depletion of ER Ca(2+) leads to overactivation of the neuronal store-operated Ca(2+) entry (nSOC) pathway in YAC128 MSN spines. The synaptic nSOC pathway is controlled by the ER resident protein STIM2. We discovered that STIM2 expression is elevated in aged YAC128 striatal cultures and in YAC128 mouse striatum. Knock-down of InsP3R1 expression by antisense oligonucleotides or knock-down or knock-out of STIM2 resulted in normalization of nSOC and rescue of spine loss in YAC128 MSNs. The selective nSOC inhibitor EVP4593 was identified in our previous studies. We now demonstrate that EVP4593 reduces synaptic nSOC and rescues spine loss in YAC128 MSNs. Intraventricular delivery of EVP4593 in YAC128 mice rescued age-dependent striatal spine loss in vivo. Our results suggest EVP4593 and other inhibitors of the STIM2-dependent nSOC pathway as promising leads for HD therapeutic development. In Huntington's disease (HD) mutant Huntingtin (mHtt) causes early corticostriatal synaptic dysfunction and eventual neurodegeneration of medium spine neurons (MSNs) through poorly understood mechanisms. We report here that corticostriatal cocultures prepared from

  12. Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Imis Dogan

    2015-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

  13. Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

    Energy Technology Data Exchange (ETDEWEB)

    Nieoullon, A; Dusticier, N [Centre National de la Recherche Scientifique, 13 - Marseille (France). Inst. de Neurophysiologie et Psychophysiologie

    1982-01-01

    The release of /sup 3/H-dopamine (DA) continuously synthesized from /sup 3/H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of /sup 3/H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to reestablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease.

  14. Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

    International Nuclear Information System (INIS)

    Nieoullon, A.; Dusticier, N.

    1982-01-01

    The release of 3 H-dopamine (DA) continuously synthesized from 3 H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of 3 H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to restablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease. (Author)

  15. Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase (STEP)

    Science.gov (United States)

    Li, Hui; Li, Kang-shuai; Su, Jing; Chen, Lai-Zhong; Xu, Yun-Fei; Wang, Hong-Mei; Gong, Zheng; Cui, Guo-Ying; Yu, Xiao; Wang, Kai; Yao, Wei; Xin, Tao; Li, Min-Yong; Xiao, Kun-Hong; An, Xiao-fei; Huo, Yuqing; Xu, Zhi-gang; Sun, Jin-Peng; Pang, Qi

    2013-01-01

    Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward pNPP, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both KIM and KIS of STEP were required for ERK interaction. In addition to the N-terminal KIS region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. PMID:24117863

  16. Role of contingency in striatal response to incentive in adolescents with anxiety.

    Science.gov (United States)

    Benson, Brenda E; Guyer, Amanda E; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

    2015-03-01

    This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

  17. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation

    International Nuclear Information System (INIS)

    Calvini, Piero; Rodriguez, Guido; Nobili, Flavio; Inguglia, Fabrizio; Mignone, Alessandro; Guerra, Ugo P.

    2007-01-01

    To design a novel algorithm (BasGan) for automatic segmentation of striatal 123 I-FP-CIT SPECT. The BasGan algorithm is based on a high-definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. A highly significant correlation was achieved between true binding potential and measured 123 I activity from the phantom. 123 I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co-registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. (orig.)

  18. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

    Science.gov (United States)

    Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

    2016-12-01

    Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos + D2 MSNs and decreased c-Fos + non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

    Science.gov (United States)

    Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

    2013-01-01

    Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

  20. Combined DaT imaging and olfactory testing for differentiating parkinsonian disorders

    DEFF Research Database (Denmark)

    Borghammer, Per; Knudsen, K; Østergaard, K

    2014-01-01

    ObjectiveDopamine transporter (DaT) imaging with single photon emission computed tomography (SPECT) detects loss of striatal dopaminergic innervation with very high sensitivity. It cannot readily distinguish idiopathic Parkinson's disease (iPD) and dementia with Lewy bodies (DLB) from atypical...... predicted a dopamine-deficient diagnosis with 98% sensitivity and 98% specificity. The combined DaT/olfactory testing correctly classified 91% of patients as iPD/DLB (PPV 91%). The PPV rose to 97% or greater in anosmic patients. In contrast, only 45% of aPD patients were categorised correctly by combined Da...

  1. Diagnostic imaging of dementia with Lewy bodies by susceptibility-weighted imaging of nigrosomes versus striatal dopamine transporter single-photon emission computed tomography: a retrospective observational study

    Energy Technology Data Exchange (ETDEWEB)

    Kamagata, Koji; Sato, Kanako; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K.; Aoki, Shigeki [Juntendo University Graduate School of Medicine, Department of Radiology, Bunkyo-ku, Tokyo (Japan); Nakatsuka, Tomoya; Inaoka, Tsutomu; Terada, Hitoshi [Toho University Sakura Medical Center, Department of Radiology, Sakura, Sakura (Japan); Sakakibara, Ryuji; Tsuyusaki, Yohei [Toho University Sakura Medical Center, Department of Neurology, Sakura, Sakura (Japan); Takamura, Tomohiro [University of Yamanashi, Department of Radiology, Chuo-shi, Yamanashi (Japan)

    2017-01-15

    The characteristics of dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and amnestic mild cognitive impairment (a-MCI) overlap but require different treatments; therefore, it is important to differentiate these pathologies. Assessment of dopamine uptake in the striatum using dopamine transporter (DaT) single-photon emission computed tomography (SPECT) is the gold standard for diagnosing DLB; however, this modality is expensive, time consuming and involves radiation exposure. Degeneration of the substantia nigra nigrosome-1, which occurs in DLB, but not in AD/a-MCI, can be identified by 3T susceptibility-weighted imaging (SWI). Therefore, the aim of this retrospective observational study was to compare SWI with DaT-SPECT for differentiation of DLB from AD/a-MCI. SWI data were acquired for patients with clinically diagnosed DLB (n = 29), AD (n = 18), a-MCI (n = 13) and healthy controls (n = 26). Images were analysed for nigrosome-1 degeneration. Diagnostic accuracy was evaluated for DLB, AD and a-MCI compared with striatal dopamine uptake using DaT-SPECT. SWI achieved 90% diagnostic accuracy (93% sensitivity, 87% specificity) for the detection of nigrosome-1 degeneration in DLB and not in AD/a-MCI as compared with 88.3% accuracy (93% sensitivity, 84% specificity) using DaT-SPECT. SWI nigrosome-1 evaluation was useful in differentiating DLB from AD/a-MCI, with high accuracy. This less invasive and less expensive method is a potential alternative to DaT-SPECT for the diagnosis of DLB. (orig.)

  2. System-Level Power Optimization for a ΣΔ D/A Converter for Hearing-Aid Application

    DEFF Research Database (Denmark)

    Pracný, Peter; Jørgensen, Ivan Harald Holger; Bruun, Erik

    2013-01-01

    This paper deals with a system-level optimization of a back-end of audio signal processing chain for hearing-aids, including a sigma-delta modulator digital-to-analog converter (DAC) and a Class D power amplifier. Compared to other stateof-the-art designs dealing with sigma-delta modulator design...... hearing-aid audio back-end system resulting in less hardware and power consumption in the interpolation filter, in the sigma-delta modulator and reduced switching rate of the Class D output stage....

  3. Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.

    Science.gov (United States)

    Thiele, Sherri L; Chen, Betty; Lo, Charlotte; Gertler, Tracey S; Warre, Ruth; Surmeier, James D; Brotchie, Jonathan M; Nash, Joanne E

    2014-11-01

    Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs

  4. Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling

    Directory of Open Access Journals (Sweden)

    Yeunkum Lee

    2017-06-01

    Full Text Available Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3-overexpressing transgenic (TG mice that display manic-like behaviors. The results of transcriptome analysis suggested that mammalian target of rapamycin complex 1 (mTORC1 signaling may be the primary molecular signature altered in the Shank3 TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared to wild-type (WT mice. To elucidate the potential underlying mechanism, we re-analyzed previously reported protein interactomes, and detected a high connectivity between Shank3 and several upstream regulators of mTORC1, such as tuberous sclerosis 1 (TSC1, TSC2 and Ras homolog enriched in striatum (Rhes, via 94 common interactors that we denominated “Shank3-mTORC1 interactome”. We noticed that, among the 94 common interactors, 11 proteins were related to actin filaments, the level of which was increased in the dorsal striatum of Shank3 TG mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1 proteins from the striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome were significantly associated with bipolar disorder (BD. Altogether, our results suggest a protein interaction-mediated connectivity between Shank3 and certain upstream

  5. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ΔFosB in mice.

    Science.gov (United States)

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ΔFosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ΔFosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ΔFosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ΔFosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ΔFosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ΔFosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Win, Maartje M.L. de; Lavini, Cristina Mphil; Heeten, Gerard J. den; Habraken, Jan

    2003-01-01

    A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand 123 I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [ 123 I]FP-CIT binding ratios of the test/retest studies were 1.7 ± 0.2 and 1.6 ± 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [ 123 I]FP-CIT binding ratios in rats is highly reproducible

  7. Pre-pulse inhibition and striatal dopamine in subjects at an ultra-high risk for psychosis

    NARCIS (Netherlands)

    de Koning, Mariken B.; Bloemen, Oswald J. N.; van Duin, Esther D. A.; Booij, Jan; Abel, Kathryn M.; de Haan, Lieuwe; Linszen, Don H.; van Amelsvoort, Thérèse A. M. J.

    2014-01-01

    Reduced prepulse inhibition (PPI) of the acoustic startle response is thought to represent a robust biomarker in schizophrenia. Reduced PPI has been demonstrated in subjects at ultra high risk (UHR) for developing psychosis. Imaging studies report disruption of striatal dopaminergic

  8. Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

    OpenAIRE

    Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

    1999-01-01

    Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

  9. Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

    Science.gov (United States)

    Lane, E L; Cheetham, S; Jenner, P

    2008-01-01

    The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

  10. Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt.

    Science.gov (United States)

    Sweitzer, Maggie M; Geier, Charles F; Denlinger, Rachel; Forbes, Erika E; Raiff, Bethany R; Dallery, Jesse; McClernon, F J; Donny, Eric C

    2016-03-01

    Tobacco smoking is associated with dysregulated reward processing within the striatum, characterized by hypersensitivity to smoking rewards and hyposensitivity to non-smoking rewards. This bias toward smoking reward at the expense of alternative rewards is further exacerbated by deprivation from smoking, which may contribute to difficulty maintaining abstinence during a quit attempt. We examined whether abstinence-induced changes in striatal processing of rewards predicted lapse likelihood during a quit attempt supported by contingency management (CM), in which abstinence from smoking was reinforced with money. Thirty-six non-treatment-seeking smokers participated in two functional MRI (fMRI) sessions, one following 24-h abstinence and one following smoking as usual. During each scan, participants completed a rewarded guessing task designed to elicit striatal activation in which they could earn smoking and monetary rewards delivered after the scan. Participants then engaged in a 3-week CM-supported quit attempt. As previously reported, 24-h abstinence was associated with increased striatal activation in anticipation of smoking reward and decreased activation in anticipation of monetary reward. Individuals exhibiting greater decrements in right striatal activation to monetary reward during abstinence (controlling for activation during non-abstinence) were more likely to lapse during CM (p reward. These results are consistent with a growing number of studies indicating the specific importance of disrupted striatal processing of non-drug reward in nicotine dependence and highlight the importance of individual differences in abstinence-induced deficits in striatal function for smoking cessation.

  11. Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

    Science.gov (United States)

    Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

    2016-03-01

    Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

  12. Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds.

    Science.gov (United States)

    Tokarev, Kirill; Hyland Bruno, Julia; Ljubičić, Iva; Kothari, Paresh J; Helekar, Santosh A; Tchernichovski, Ofer; Voss, Henning U

    2017-08-11

    In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate's song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

  13. Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L--Tyrosine PET

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    Claire E. Wilcox

    2010-01-01

    Full Text Available Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[18F]-fluoro-L--tyrosine (FMT positron emission tomography (PET uptake in striatal subregions was correlated with BMI (kg/m2 and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (=.05. These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

  14. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

    2012-01-01

    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  15. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  16. Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior.

    Science.gov (United States)

    Burke, Mary V; Small, Dana M

    2016-06-01

    Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

  17. Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability

    OpenAIRE

    Miller, Michael L.; Ren, Yanhua; Szutorisz, Henrietta; Warren, Noël A.; Tessereau, Chloé; Egervári, Gábor; Mlodnicka, Agnieszka; Kapoor, Manav; Chaarani, Bader; Morris, Claudia V.; Schumann, Gunter; Garavan, Hugh; Goate, Alison M.; Bannon, Michael J.; Halperin, Jeffrey M.

    2017-01-01

    Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood. Here we report the critical role of ventral striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vulnerability. Using an ADHD rat mode...

  18. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

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    Marios Politis

    2017-01-01

    Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

  19. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments

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    Jill R. Crittenden

    2011-09-01

    Full Text Available The striatum is composed principally of GABAergic, medium spiny projection neurons (MSNs that can be categorized based on their gene expression, electrophysiological profiles and input-output circuits. Major subdivisions of MSN populations include 1 those in ventromedial and dorsolateral striatal regions, 2 those giving rise to the direct and indirect pathways, and 3 those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input-output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in

  20. Concomitant Appearance of Pisa Syndrome and Striatal Hand in Parkinson’s Disease

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    Sanjay Pandey

    2011-10-01

    Full Text Available Pisa syndrome is (PS usually seen in patients receiving antipsychotic drugs and characterised by lateral flexion of trunk and axial dystonia. It is believed that antipsychotic drugs lead to dopamine blockage causing PS. We describe a Parkinson’s disease patient who was doing well with levodopa/carbidopa for 3 years and developed lateral flexion of trunk. His abnormal posture used to completely improve upon lying down position. He also had striatal hand deformity suggestive of focal dystonia.

  1. Prolonged striatal disinhibition as a chronic animal model of tic disorders.

    Science.gov (United States)

    Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

    2017-12-01

    Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

  3. Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats.

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    Qiqi Feng

    Full Text Available Huntington's disease (HD is a neurological degenerative disease and quinolinic acid (QA has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv+ and neuropeptide Y (NPY+ interneurons were both significantly reduced while those of calretinin (Cr+ and choline acetyltransferase (ChAT+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD.

  4. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  5. A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

    Energy Technology Data Exchange (ETDEWEB)

    Vanzi, Eleonora; De Cristofaro, Maria T.; Sotgia, Barbara; Mascalchi, Mario; Formiconi, Andreas R. [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2007-09-15

    The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-{beta}-carboxymethoxy-3-{beta}-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs. (orig.)

  6. Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell–derived medium spiny neurons

    Directory of Open Access Journals (Sweden)

    Marco Straccia

    Full Text Available A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening.

  7. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

    Science.gov (United States)

    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-02-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  8. Electrical and chemical transmission between striatal GABAergic output neurones in rat brain slices

    Science.gov (United States)

    Venance, Laurent; Glowinski, Jacques; Giaume, Christian

    2004-01-01

    Basal ganglia are interconnected subcortical nuclei, connected to the thalamus and all cortical areas involved in sensory motor control, limbic functions and cognition. The striatal output neurones (SONs), the major striatal population, are believed to act as detectors and integrators of distributed patterns of cerebral cortex inputs. Despite the key role of SONs in cortico-striatal information processing, little is known about their local interactions. Here, we report the existence and characterization of electrical and GABAergic transmission between SONs in rat brain slices. Tracer coupling (biocytin) incidence was high during the first two postnatal weeks and then decreased (postnatal days (P) 5–25, 60%; P25–30, 29%; n = 61). Electrical coupling was observed between 27% of SON pairs (coupling coefficient: 3.1 ± 0.3%, n = 89 at P15) and as shown by single-cell RT-PCR, several connexin (Cx) mRNAs were found to be expressed (Cx31.1, Cx32, Cx36 and Cx47). GABAergic synaptic transmission (abolished by bicuculline, a GABAA receptor antagonist) observed in 19% of SON pairs (n = 62) was reliable (mean failure rate of 6 ± 3%), precise (variation coefficient of latency, 0.06), strong (IPSC amplitudes of 38 ± 12 pA) and unidirectional. Interestingly, electrical and chemical transmission were mutually exclusive. These results suggest that preferential networks of electrically and chemically connected SONs, might be involved in the channelling of cortico-basal ganglia information processing. PMID:15235091

  9. Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

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    Alex G. Lee

    2016-06-01

    Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  10. Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

    Science.gov (United States)

    Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

    2017-07-01

    Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

    Directory of Open Access Journals (Sweden)

    Bart P de Kwaasteniet

    Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

  12. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

    Science.gov (United States)

    Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

    2017-03-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  13. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder.

    Science.gov (United States)

    Herbort, Maike C; Soch, Joram; Wüstenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, Jürgen; Walter, Henrik; Roepke, Stefan; Schott, Björn H

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

  14. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

    Science.gov (United States)

    Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

    2015-12-07

    Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

  15. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

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    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  16. Rapid eye movement sleep behaviour disorder and striatal dopamine depletion in patients with Parkinson's disease.

    Science.gov (United States)

    Chung, S J; Lee, Y; Lee, J J; Lee, P H; Sohn, Y H

    2017-10-01

    Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion. A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan. Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less-affected side and axial symptoms, and were prescribed higher levodopa-equivalent doses at follow-up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less-affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables. These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism. © 2017 EAN.

  17. Age related changes in striatal resting state functional connectivity in autism

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    Aarthi ePadmanabhan

    2013-11-01

    Full Text Available Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity with resting state fMRI from late childhood to early adulthood (8-36 years, using a seed based functional connectivity method with the striatum. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to TD participants. In addition, ASD participants showed aberrant age-related changes in connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g. fusiform gyrus, inferior and superior temporal gyri. In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which also may help clarify discrepant findings in the literature.

  18. Postural & striatal deformities in Parkinson`s disease: Are these rare?

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    Sanjay Pandey

    2016-01-01

    Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

  19. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

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    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  20. Increased coherence among striatal regions in the theta range during attentive wakefulness

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    G. Lepski

    2012-08-01

    Full Text Available The striatum, the largest component of the basal ganglia, is usually subdivided into associative, motor and limbic components. However, the electrophysiological interactions between these three subsystems during behavior remain largely unknown. We hypothesized that the striatum might be particularly active during exploratory behavior, which is presumably associated with increased attention. We investigated the modulation of local field potentials (LFPs in the striatum during attentive wakefulness in freely moving rats. To this end, we implanted microelectrodes into different parts of the striatum of Wistar rats, as well as into the motor, associative and limbic cortices. We then used electromyograms to identify motor activity and analyzed the instantaneous frequency, power spectra and partial directed coherence during exploratory behavior. We observed fine modulation in the theta frequency range of striatal LFPs in 92.5 ± 2.5% of all epochs of exploratory behavior. Concomitantly, the theta power spectrum increased in all striatal channels (P 0.7 between the primary motor cortex and the rostral part of the caudatoputamen nucleus, as well as among all striatal channels (P < 0.001. Conclusively, we observed a pattern of strong theta band activation in the entire striatum during attentive wakefulness, as well as a strong coherence between the motor cortex and the entire striatum. We suggest that this activation reflects the integration of motor, cognitive and limbic systems during attentive wakefulness.

  1. High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

    Science.gov (United States)

    Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

    2013-09-01

    Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

  2. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Science.gov (United States)

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  3. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  4. A simple algorithm for subregional striatal uptake analysis with partial volume correction in dopaminergic PET imaging

    International Nuclear Information System (INIS)

    Lue Kunhan; Lin Hsinhon; Chuang Kehshih; Kao Chihhao, K.; Hsieh Hungjen; Liu Shuhsin

    2014-01-01

    In positron emission tomography (PET) of the dopaminergic system, quantitative measurements of nigrostriatal dopamine function are useful for differential diagnosis. A subregional analysis of striatal uptake enables the diagnostic performance to be more powerful. However, the partial volume effect (PVE) induces an underestimation of the true radioactivity concentration in small structures. This work proposes a simple algorithm for subregional analysis of striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging. The PVC algorithm analyzes the separate striatal subregions and takes into account the PVE based on the recovery coefficient (RC). The RC is defined as the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration, and is derived from a combination of the traditional volume of interest (VOI) analysis and the large VOI technique. The clinical studies, comprising 11 patients with Parkinson's disease (PD) and 6 healthy subjects, were used to assess the impact of PVC on the quantitative measurements. Simulations on a numerical phantom that mimicked realistic healthy and neurodegenerative situations were used to evaluate the performance of the proposed PVC algorithm. In both the clinical and the simulation studies, the striatal-to-occipital ratio (SOR) values for the entire striatum and its subregions were calculated with and without PVC. In the clinical studies, the SOR values in each structure (caudate, anterior putamen, posterior putamen, putamen, and striatum) were significantly higher by using PVC in contrast to those without. Among the PD patients, the SOR values in each structure and quantitative disease severity ratings were shown to be significantly related only when PVC was used. For the simulation studies, the average absolute percentage error of the SOR estimates before and after PVC were 22.74% and 1.54% in the healthy situation, respectively; those in the neurodegenerative situation were 20.69% and 2

  5. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  6. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  7. Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

    2016-05-01

    Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

  8. Avaliação dos níveis séricos de testosterona em pacientes com síndrome da apneia obstrutiva do sono Evaluation of testosterone serum levels in patients with obstructive sleep apnea syndrome

    Directory of Open Access Journals (Sweden)

    Fernando Drimel Molina

    2011-02-01

    Full Text Available Homens com síndrome da apneia obstrutiva do sono (SAOS podem apresentar diminuição dos níveis de testosterona devido à hipóxia. OBJETIVOS: Relacionar os níveis séricos da testosterona, em pacientes com SAOS, com parâmetros clínico-laboratoriais. MATERIAL E MÉTODOS: Foram revisados 103 prontuários de pacientes com SAOS, entre os anos de 2002 e 2009, e coletados os seguintes dados: idade à época da realização da polissonografia, valores do Hematócrito e Hemoglobina, nível sérico da testosterona total, IMC, índice de apneia/hipopneia(IAH e SatO2. FORMA DO ESTUDO: Estudo de casos retrospectivo em corte transversal. RESULTADOS: 79 pacientes (77% não apresentaram alteração hormonal e 24 (23% apresentaram níveis séricos inferiores. Dos pacientes com testosterona normal 70% estavam com sobrepeso, enquanto que 63% com testosterona alterada apresentaram obesidade grau I (pMales with obstructive sleep apnea syndrome (OSAS may present decreased testosterone serum levels because of hypoxemia. AIM: To correlate testosterone levels in OSAS patients with laboratory parameters. MATERIAL AND METHODS: 103 registries of OSAS patients were reviewed from 2002 to 2009. The following data collected: age when polysomnography was done, hematocrit and hemoglobin levels, total testosterone serum levels, BMI, apnea/hypopnea index (AHI, and O2 saturation. STUDY DESIGN: A cross-sectional retrospective case study. RESULTS: 79 patients (77% had no hormonal changes, and 24 patients (23% had decreased serum levels. In patients with normal testosterone levels, 70% were overweight; 63% with altered testosterone levels had obesity grade I (p<0.05. Patients with altered testosterone levels had significantly lower average doses of Ht, Hb and androgen compared to patients without altered androgen levels. The average BMI of patients with altered hormone levels was significantly higher compared to patients with normal hormone levels. CONCLUSIONS: The relationship

  9. ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).

    Science.gov (United States)

    Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko; Matsuzaki, Hideo; Brody, A Harrison; Wu, Terence; Greengard, Paul; Taylor, Jane R; Nairn, Angus C

    2017-03-08

    ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We

  10. Karol Wojtyla e os níveis de sentido da regra de ouro = Karol Wojtyla and the levels of meaning of the golden rule

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    Salles, Sergio de Souza

    2014-01-01

    Full Text Available A regra de ouro, o princípio ético segundo o qual devemos fazer aos outros o que nós queremos que nos façam, é também conhecida na tradição cristã como regra de amor ao próximo. O objetivo do presente artigo é examinar a relação entre dois níveis de sentido da regra de ouro nas investigações filosóficas de Karol Wojtyla, anteriores ao seu pontificado. Uma vertente do atual debate sobre a regra de ouro diz respeito às suas raízes antropológicas e ao seu sentido ético. A abordagem filosófica de Karol Wojtyla da regra de ouro perpassa tanto a investigação de suas raízes antropológicas quanto de suas exigências éticas. Com efeito, há um sentido pré-ético da regra de ouro em Karol Wojtyla, que está vinculado à sua abordagem fenomenológica da pessoa humana e da vida em comunidade. Nesse nível, a regra de ouro é descrita a partir da lógica da autorrealização, que manifesta o valor personalista da ação humana. Por outro lado, há também um segundo sentido propriamente ético da regra de ouro, graças ao qual desenvolve sua perspectiva da doação de si como condição da realização de si mesmo. Nessa perspectiva wojtyliana, o que torna uma regra moral áurea é a sua capacidade de integrar e complementar a busca pela própria realização com a realização do outro mediante a doação de si mesmo

  11. Right anterior cingulate cortical thickness and bilateral striatal volume correlate with child behavior checklist aggressive behavior scores in healthy children.

    Science.gov (United States)

    Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D; Evans, Alan C; Karama, Sherif

    2011-08-01

    The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Avaliação do dímero D (D-Di na doença hipertensiva específica da gravidez (DHEG D-dimer plasma levels assessment in preeclampsia

    Directory of Open Access Journals (Sweden)

    Luci Maria Sant'Ana Dusse

    2003-09-01

    Full Text Available A doença hipertensiva específica da gravidez (DHEG, na sua forma pura, caracteriza-se pelo aparecimento, em grávida normotensa, após a vigésima semana de gestação, da tríade sintomática: hipertensão, proteinúria e edema. A DHEG está associada a vasoconstrição generalizada, anormalidades da coagulação e deposição de fibrina na microcirculação da placenta. A fibrina compromete a perfusão adequada da placenta, contribuindo para a prematuridade, o baixo peso fetal e a mortalidade neonatal. Os dímeros D (D-Di constituem os menores fragmentos dos produtos de degradação da fibrina (pdf e são produzidos após a lise, pela plasmina, da ligação cruzada da fibrina. Níveis plasmáticos aumentados de D-Di indicam tanto uma exacerbação da formação de fibrina como um aumento da ação da plasmina. O presente trabalho teve por objetivo avaliar e comparar os níveis plasmáticos de D-Di, obtido por Elisa (Stago em gestantes-controle (n = 26, gestantes com DHEG nas formas leve e moderada (n = 23 e gestantes com DHEG na forma grave (n = 20, visando a investigar a possível utilização desse marcador laboratorial para diagnóstico e/ou prognóstico da doença. As médias e os desvios padrões obtidos para os três grupos avaliados foram 1.146,6 ± 311,2; 1.060,3 ± 259,2 e 1.497,8 ± 435,3ng/ml, respectivamente. A análise estatística das médias dos resultados obtidos revelou um aumento significativo de D-Di plasmático no grupo com DHEG grave, comparando-se aos grupos com DHEG leve/moderada (p Preeclampsia is associated to a generalized vasoconstriction, clot abnormalities and fibrin deposition within placenta microcirculation. The presence of fibrin hampers the placenta perfusion contributing to prematurity, fetal low weight and neonates' mortality. D-Dimers (D-Di are the products of degradation of cross-linked fibrin by plasmin. Increased plasma levels of D-Di may indicate either an exacerbated fibrin formation or an increase

  13. Procedimento fuzzy aplicado à avaliação da insalubridade em atividades agrícolas Fuzzy procedure applied to evaluate the insalubrity level in agriculture activities

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    Tadayuki Yanagi Junior

    2012-06-01

    Full Text Available Diante do alto grau de mecanização a que as atividades agrícolas estão sendo submetidas, objetivou-se, com esta pesquisa, desenvolver um modelo fuzzy capaz de avaliar e classificar o nível de insalubridade em diversos ambientes de trabalho. O modelo desenvolvido tem como variáveis de entrada: o índice de bulbo úmido e temperatura de globo (IBUTG, °C, o nível de ruído (dBA, a taxa de metabolismo (W m-2 e o tempo de descanso (% e, como variável de saída, o índice de bem-estar humano (IBEH. O método de inferência utilizado foi o de Mandani e, na defuzificacão, utilizou-se o método do centro de gravidade. O sistema de regras foi desenvolvido com base nas combinações das variáveis de entrada. Foram definidas 400 regras com pesos iguais a 1, sendo que, na elaboração das regras, um especialista da área foi consultado. Foram utilizados dados de campo visando a testar o sistema desenvolvido, e os resultados mostraram que a modelagem proposta é uma ferramenta promissora na determinação do IBEH, apresentando tempo de descanso ideal variando de 64,2% (motosserra, próximo ao ouvido do operador até 25% (derriçadora, 20 m de distância do operador, sendo que, diante de um cenário predefinido do ambiente térmico e acústico, foi possível determinar o grau de bem-estar humano e o tempo de descanso ideal para cada equipamento avaliado.Given the high degree of mechanization to which agricultural activities are being submitted, the objective of this research was to develop a fuzzy model able to evaluate and classify the insalubrity level in different work environments. The model developed has as input variables: wet bulb globe temperature index (WBGTI, °C, noise level (dBA, metabolic rate (W m-2 and rest time (%; and has as output variable the human well-being index (HWBI. The Mamdani inference method was used, and for the defuzzification, the Center of Gravity method was used. The system of rules was developed based on

  14. Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

    Science.gov (United States)

    Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

    2016-06-01

    Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0

  15. Morphological and metabolic changes in the nigro-striatal pathway of synthetic proteasome inhibitor (PSI-treated rats: a MRI and MRS study.

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    Stefano Delli Pizzi

    Full Text Available Systemic administration of a Synthetic Proteasome Inhibitor (PSI in rats has been described as able to provide a model of Parkinson's disease (PD, characterized by behavioral and biochemical modifications, including loss of dopaminergic neurons in the substantia nigra (SN, as assessed by post-mortem studies. With the present study we aimed to assess in-vivo by Magnetic Resonance (MR possible morphological and metabolic changes in the nigro-striatal pathway of PSI-treated rats. 10 animals were subcutaneously injected with PSI 6.0 mg/kg dissolved in DMSO 100%. Injections were made thrice weekly over the course of two weeks. 5 more animals injected with DMSO 100% with the same protocol served as controls. The animals underwent MR sessions before and at four weeks after the end of treatment with either PSI or vehicle. MR Imaging was performed to measure SN volume and Proton MR Spectroscopy ((1H-MRS was performed to measure metabolites changes at the striatum. Animals were also assessed for motor function at baseline and at 4 and 6 weeks after treatment. Dopamine and dopamine metabolite levels were measured in the striata at 6 weeks after treatment. PSI-treated animals showed volumetric reduction of the SN (p<0.02 at 4 weeks after treatment as compared to baseline. Immunofluorescence analysis confirmed MRI changes in SN showing a reduction of tyrosine hydroxylase expression as compared to neuron-specific enolase expression. A reduction of N-acetyl-aspartate/total creatine ratio (p = 0.05 and an increase of glutamate-glutamine-γ amminobutirrate/total creatine were found at spectroscopy (p = 0.03. At 6 weeks after treatment, PSI-treated rats also showed motor dysfunction compared to baseline (p = 0.02, accompanied by dopamine level reduction in the striatum (p = 0.02. Treatment with PSI produced morphological and metabolic modifications of the nigro-striatal pathway, accompanied by motor dysfunction. MR demonstrated to be a powerful mean to assess in

  16. Striatal Dopamine Depletion Patterns and Early Non-Motor Burden in Parkinsons Disease.

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    Su Jin Chung

    Full Text Available The mechanism underlying non-motor symptoms in Parkinson's disease has not yet been elucidated. In this study, we hypothesized that Parkinson patients with more non-motor symptoms have a different pattern of striatal dopamine depletion, particularly in areas other than the sensorimotor striatum, compared to those with fewer non-motor symptoms.We conducted a prospective survey of the degree of non-motor symptoms (using the Korean version of the Non-Motor Symptoms Scale; K-NMSS in 151 patients with early-stage Parkinson's disease who had undergone a dopamine transporter PET scan as an initial diagnostic procedure. We classified the patients into two groups; high non-motor patients (HNM-PD; K-NMSS score ≥ 41 and low non-motor patients (LNM-PD.Patients in the HNM-PD group (n = 71 were older, had longer symptom duration, exhibited more severe motor deficits, and had been prescribed higher levodopa-equivalent doses at follow-up than those in the LNM-PD group. However, dopamine transporter binding to the striatal sub-regions and inter-sub-regional binding ratios were comparable between the two groups. A general linear model showed that the HNM-PD group had significantly more severe motor deficits than the LNM-PD group after controlling for age, gender, symptom duration, and dopamine transporter binding to the sensorimotor striatum.This study demonstrated that the pattern of striatal dopamine depletion does not contribute to early non-motor burden in Parkinson's disease. Our results suggest that LNM-PD patients may have a more benign course of motor symptom progression than HNM-PD patients.

  17. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

    Science.gov (United States)

    Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

    2013-09-11

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

  18. Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

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    Andreas eKlaus

    2011-07-01

    Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

  19. Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal Excitation Leads to Tremor.

    Science.gov (United States)

    Oran, Yael; Bar-Gad, Izhar

    2018-02-14

    Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum. The tremor was accompanied by coherent oscillations in the local field potential (LFP). Individual neuron activity patterns became oscillatory and coherent in the tremor frequency. Striatal neurons, but not GP neurons, displayed additional temporal, nonoscillatory correlations. The subsequent reduction in the corticostriatal input following muscimol injection to the corresponding somatotopic location in the primary motor cortex led to disruption of the tremor and a reduction of the LFP oscillations and individual neuron's phase-locked activity. The breakdown of the normal balance of excitation and inhibition in the striatum has been shown previously to be related to different motor abnormalities. Our results further indicate that the balance between excitatory corticostriatal input and feedforward FSI inhibition is sufficient to break down the striatal decorrelation process and generate oscillations resulting in rest tremor typical of multiple basal ganglia disorders. SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs) play a key role in normal striatal processing by exerting powerful inhibitory control over the network. FSI malfunctions have been associated with abnormal processing of information within the striatum that leads to multiple movement disorders. Here, we study the changes in neuronal activity and movement kinematics following selective inhibition of these

  20. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

    Science.gov (United States)

    Sameiro-Barbosa, Catia M; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system.

  1. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  2. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation

    Science.gov (United States)

    Sameiro-Barbosa, Catia M.; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  3. Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Cumming, Paul

    2007-01-01

     The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...... was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant...... depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1...

  4. COMT Val(158) met genotype and striatal D(2/3) receptor binding in adults with 22q11 deletion syndrome.

    LENUS (Irish Health Repository)

    Boot, Erik

    2011-09-01

    Although catechol-O-methyltransferase (COMT) activity evidently affects dopamine function in prefrontal cortex, the contribution is assumed less significant in striatum. We studied whether a functional polymorphism in the COMT gene (Val(158) Met) influences striatal D(2\\/3) R binding ratios (D(2\\/3) R BP(ND) ) in 15 adults with 22q11 deletion syndrome and hemizygous for this gene, using single photon emission computed tomography and the selective D(2\\/3) radioligand [(123) I]IBZM. Met hemizygotes had significantly lower mean D(2\\/3) R BPND than Val hemizygotes. These preliminary data suggest that low COMT activity may affect dopamine levels in striatum in humans and this may have implications for understanding the contribution of COMT activity to psychiatric disorders.

  5. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  6. Striatal abnormalities in trichotillomania: A multi-site MRI analysis

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    Masanori Isobe

    2018-01-01

    Full Text Available Trichotillomania (hair-pulling disorder is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N = 68 individuals with trichotillomania and N = 41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

  7. Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

    Science.gov (United States)

    Snyder-Keller, A; Costantini, L C; Graber, D J

    2001-01-01

    Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

  8. Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

    Science.gov (United States)

    Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

    2016-03-01

    Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

  9. Interaction of structural analogs of dopamine, chlorpromazine and sulpiride with striatal dopamine receptors

    International Nuclear Information System (INIS)

    Wallace, R.A.

    1987-01-01

    The objectives of these studies were to determine if the nitrogen atom of dopaminergic agonists and antagonists drugs is required for interaction with the D-1 and D-2 dopamine receptors and whether the positively charged or uncharged molecular species interacts with these receptors. To address these issues, permanently charged analogs of dopamine, chlorpromazine and sulpiride were synthesized in which a dimethylsulfonium, dimethylselenonium or quaternary ammonium group replaced the amine group. Permanently uncharged analogs which contained a methylsulfide, methylselenide and sulfoxide group instead of an amine group were also synthesized. The interactions of these compounds with striatal dopamine receptors were studied. We found that the permanently charged dopamine analogs bound to the D-2 receptor of striatal membranes like conventional dopaminergic agonists and displayed agonist activity at the D-2 receptor regulating potassium-evoked [ 3 H] acetylcholine release. In contrast, the permanently uncharged analogs bound only to the high affinity state of the D-2 receptor and had neither agonist or antagonist activity

  10. Selective updating of working memory content modulates meso-cortico-striatal activity.

    Science.gov (United States)

    Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

    2011-08-01

    Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

  11. Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability.

    Science.gov (United States)

    Damasceno, Alfredo; Damasceno, Benito Pereira; Cendes, Fernando

    2016-05-01

    MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Forty-nine relapsing-remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue. © The Author(s), 2015.

  12. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  13. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease

    International Nuclear Information System (INIS)

    Tanaka, Yasuhiro; Meguro, Kenichi; Yamaguchi, Satoshi

    2003-01-01

    Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D 2 receptor density in Alzheimer's disease (AD). Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [ 11 C]raclopride (D 2 antagonist). The uptake of [ 11 C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD. (author)

  14. KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

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    M. Belén Pérez-Ramírez

    2015-01-01

    Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

  15. Impulsivity in Parkinson’s Disease Is Associated With Alterations in Affective and Sensorimotor Striatal Networks

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    Marit F. L. Ruitenberg

    2018-04-01

    Full Text Available A subset of patients with Parkinson’s disease (PD experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD.

  16. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    Science.gov (United States)

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  17. Phasic dopamine release drives rapid activation of striatal D2-receptors

    Science.gov (United States)

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  18. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  19. Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

    Science.gov (United States)

    Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

    2015-02-01

    Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Interaction between striatal volume and DAT1 polymorphism predicts working memory development during adolescence

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    F. Nemmi

    2018-04-01

    Full Text Available There is considerable inter-individual variability in the rate at which working memory (WM develops during childhood and adolescence, but the neural and genetic basis for these differences are poorly understood. Dopamine-related genes, striatal activation and morphology have been associated with increased WM capacity after training. Here we tested the hypothesis that these factors would also explain some of the inter-individual differences in the rate of WM development.We measured WM performance in 487 healthy subjects twice: at age 14 and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of five single nucleotide polymorphisms (SNPs in or close to the dopamine genes DRD2, DAT-1 and COMT, which have previously been associated with gains in WM after WM training. We then analyzed which biological factors predicted the rate of increase in WM between ages 14 and 19.We found a significant interaction between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC heterozygotes with a larger putamen at age 14 showed greater WM improvement at age 19.The effect of the DAT1 polymorphism on WM development was exerted in interaction with striatal morphology. These results suggest that development of WM partially share neuro-physiological mechanism with training-induced plasticity. Keywords: Working memory, Development, Dopamine, Striatum, DAT-1, rs40184

  1. Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

    Science.gov (United States)

    Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

    2016-04-01

    Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

  2. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  3. Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study

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    Pitcher Toni L

    2012-08-01

    Full Text Available Abstract Background The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease (PD is still poorly understood. Methods High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Results Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001 and putamen volumes by 8.1% (p = 0.025. PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Conclusion Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.

  4. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    Science.gov (United States)

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

  5. Perineuronal nets play a role in regulating striatal function in the mouse.

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    Hyunchul Lee

    Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  6. Perineuronal nets play a role in regulating striatal function in the mouse.

    Science.gov (United States)

    Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu

    2012-01-01

    The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  7. Avaliação do Nível de Estresse da Equipe de Enfermagem em Terapia Intensiva/Evaluation of Stress Level Team Nursing in Intensive Care

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    Patrícia Costa dos Santos da Silva

    2012-12-01

    Full Text Available Objetivo: Avaliar o nível de estresse da equipe de enfermagem que atua em Terapia Intensiva, em um Hospital Universitário do Sul de Minas Gerais. Materiais e Métodos: Trata-se de um estudo descritivo, transversal, de abordagem quantitativa, aprovado pelo Comitê de Ética sob o Parecer nº 48/2011, desenvolvido em uma Unidade de Terapia Intensiva.A amostra constituiu-se de 20 profissionais de enfermagem. Para coleta de dados utilizou-se um questionário com questões semi-estruturadas e o Inventário de Sintomas de Stress para adultos de Lipp. Resultados: Verificou-se que a maioria dos sujeitos encontra-se na faixa etária de 20 a 30 anos (50%. Diante das situações de estresse, notou-se que 55% dos profissionais encontram-se na fase de resistência. A equipe considerou muito desgastante o relacionamento com outras unidades e supervisores (15%, a previsão e reposição de materiais (25%, assistência de enfermagem (10% e as condições de trabalho (10%. Conclusão: O estudo demonstra que a maioria dos profissionais de enfermagem atuante em terapia intensiva, apresenta sinais e sintomas de estresse, principalmente, na fase de resistência. Objective: To evaluate the stress level of the nursing team that works in the Intensive Care Unit in a School Hospital in southern Minas Gerais. Materials and Methods: This is a descriptive transversal study with a quantitative approach, approved by the Ethics Committee under the Opinion n. 48/2011, developed in an intensive care unit. The sample was consisted of 20 nurses. For data collection a questionnaire with semi-structured questions andthe Symptoms of Stress Inventory for adults Lipp was used . Results: It has beenfound that most subjects are aged 20 to 30 years (50%. In the face of stressful situations, it was noted that 55% of professionals are at the stage of resistance. The team considered to be very stressful the relationship with other units and supervisors (15%, forecasting and replenishment

  8. Eficácia da aromaterapia na redução de níveis de estresse e ansiedade em alunos de graduação da área da saúde: estudo preliminar Effectiveness of aromatherapy in reducing stress and anxiety levels in undergraduate health science students: a preliminary study

    Directory of Open Access Journals (Sweden)

    Cassandra Santantonio de Lyra

    2010-03-01

    Full Text Available Este estudo teve como objetivo verificar a eficácia de aromaterapia na diminuição de níveis de estresse e ansiedade (traço e estado de alunos de graduação de cursos na área da saúde. Participaram do estudo 36 sujeitos, com idade entre 18 e 29 anos, que foram divididos entre os que receberam tratamento (grupo aroma, n=18 e o grupo controle (n=18. Os sujeitos foram avaliados quanto a níveis de estresse e ansiedade antes e após o período de intervenção, pela Lista de Sintomas de Estresse e pelo Inventário de Ansiedade Traço e Estado. O tratamento de aromaterapia consistiu em sete sessões (duas vezes por semana de dez minutos de inalação com uma sinergia de óleos essenciais elaborada especificamente. Os escores de estresse e ansiedade antes e depois do tratamento foram comparados estatisticamente, com nível de significância de 5% (pThe purpose of this study was to assess the efficacy of aromatherapy in decreasing stress and anxiety levels in undergraduate health science students. Thirty-six students aged 18 to 29 were divided into those who received treatment (aroma group, n=18 and a control group (n=18. All subjects were assessed as to stress and anxiety levels before and after the treatment, by means of the List of Stress Symptoms and the State-Trait Anxiety Inventory. The aromatherapy treatment consisted in twice weekly, 10-minute inhalations of a synergy of essential oils made specifically for this study, for a total of 7 sessions. Stress and anxiety scores measured before and after treatment were statistically compared, with significance level set at 5% (p<0.05. The aroma group showed a significant (p<0,05 decrease in stress (less 24% and anxitey (less 13% and 19% levels, while in control group only a significant, though lesser (11% stress level decrease could be noticed. Aromatherapy thus proved effective in reducing stress and anxiety levels in graduate health students, but there is still great need to further studies to

  9. Níveis de salinidade e manejo da fertirrigação sobre características da berinjela cultivada em ambiente protegido Levels of salinity and fertigation management on the characteristics of the eggplant when grown in a protected environment

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    Everaldo Moreira da Silva

    2013-03-01

    Full Text Available Objetivou-se estudar os efeitos de diferentes níveis de salinidade do solo sobre as variáveis fenológicas e de produção da berinjela, cultivada em vasos e em ambiente protegido. O estudo foi conduzido na área experimental do Departamento de Engenharia de Biossistemas da ESALQ/USP, Piracicaba, SP. Os tratamentos foram compostos da combinação de dois fatores: 6 níveis de salinidade inicial do solo (S1 = 1,3; S2 = 2,4; S3 = 3,6; S4 = 4,5; S5 = 5,6 e S6 = 6,4 dS m-1 e dois manejos de fertirrigação: com controle da condutividade elétrica da solução do solo (M1, e o tradicional (M2, obedecendo a curva de absorção de nutrientes da cultura. O delineamento estatístico adotado foi o de blocos casualizados completos, com quatro repetições, arranjados no esquema fatorial 6 x 2. Os resultados revelaram que os níveis de salinidade do solo afetaram diretamente as variáveis, produção de matéria seca, produção de frutos e índice de área foliar das plantas. Verificou-se que a redução média na produção da cultura da berinjela, em estufa, foi da ordem de 8,65% para o incremento de 1 dS m-1 na salinidade do solo, acima da salinidade limiar, que foi de 1,71 dS m-1.The objective was to study the effects of different levels of soil salinity on the phenological variables and production of the eggplant when grown in pots in a protected environment. The study was carried out at the experimental site of the Department of Biosystems Engineering ESALQ/USP in Piracicaba, São Paulo. The treatments consisted of a combination of two factors: six initial levels of soil salinity (S1 = 1.3, S2 = 2.4, S3 = 3.6, S4 = 4.5, S5 = 5.6 and S6 = 6.4 dS m-1 and two fertigation management: with the electrical conductivity of the soil solution being controlled (M1 and traditional (M2, following the absorption curve of nutrients from the culture. The statistical design adopted was a randomized complete-block design with four replications, arranged in a 6 x 2

  10. Single versus multiple impulse control disorders in Parkinson's disease: an ¹¹C-raclopride positron emission tomography study of reward cue-evoked striatal dopamine release.

    Science.gov (United States)

    Wu, Kit; Politis, Marios; O'Sullivan, Sean S; Lawrence, Andrew D; Warsi, Sarah; Bose, Subrata; Lees, Andrew J; Piccini, Paola

    2015-06-01

    Impulse control disorders (ICDs) are reported in Parkinson's disease (PD) in association with dopaminergic treatment. Approximately 25 % of patients with ICDs have multiple co-occurring ICDs (i.e. more than one diagnosed ICD). The extent to which dopaminergic neurotransmission in PD patients with multiple ICDs differs from those with only one diagnosed ICD is unknown. The aims of this study are: (1) to investigate dopamine neurotransmission in PD patients diagnosed with multiple ICDs, single ICDs and non-ICD controls in response to reward-related visual cues using positron emission tomography with (11)C-raclopride. (2) to compare clinical features of the above three groups. PD individuals with mulitple ICDs (n = 10), single ICD (n = 7) and no ICDs (n = 9) were recruited and underwent two positron emission tomography (PET) scans with (11)C-raclopride: one where they viewed neutral visual cues and the other where they viewed a range of visual cues related to different rewards. Individuals with both multiple ICDs and single ICDs showed significantly greater ventral striatal dopamine release compared to non-ICD PD individuals in response to reward cues, but the two ICD groups did not differ from each other in the extent of dopamine release. Subjects with multiple ICDs were, however, significantly more depressed, and had higher levels of impulsive sensation-seeking compared to subjects with single ICDs and without ICDs. This is the first study to compare dopamine neurotransmission using PET neuroimaging in PD subjects with multiple vs. single ICDs. Our results suggest that striatal dopamine neurotransmission is not directly related to the co-occurrence of ICDs in PD, potentially implicating non-dopaminergic mechanisms linked to depression; and suggest that physicians should be vigilant in managing depression in PD patients with ICDs.

  11. Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats.

    Science.gov (United States)

    Azkona, Garikoitz; Sagarduy, Ainhoa; Aristieta, Asier; Vazquez, Nerea; Zubillaga, Verónica; Ruíz-Ortega, José Angel; Pérez-Navarro, Esther; Ugedo, Luisa; Sánchez-Pernaute, Rosario

    2014-04-01

    Dopamine replacement with l-DOPA is the most effective therapy in Parkinson's disease. However, with chronic treatment, half of the patients develop an abnormal motor response including dyskinesias. The specific molecular mechanisms underlying dyskinesias are not fully understood. In this study, we used a well-characterized animal model to first establish the molecular differences between rats that did and did not develop dyskinesias. We then investigated the molecular substrates implicated in the anti-dyskinetic effect of buspirone, a 5HT1A partial agonist. Striatal protein expression profile of dyskinetic animals revealed increased levels of the dopamine receptor (DR)D3, ΔFosB and phospho (p)CREB, as well as an over-activation of the DRD1 signalling pathway, reflected by elevated ratios of phosphorylated DARPP32 and ERK2. Buspirone reduced the abnormal involuntary motor response in dyskinetic rats in a dose-dependent fashion. Buspirone (4 mg/kg) dramatically reduced the presence and severity of dyskinesias (by 83%) and normalized DARPP32 and ERK2 phosphorylation ratios, while the increases in DRD3, ΔFosB and pCREB observed in dyskinetic rats were not modified. Pharmacological experiments combining buspirone with 5HT1A and DRD3 antagonists confirmed that normalization of both pDARPP32 and pERK2 is required, but not sufficient, for blocking dyskinesias. The correlation between pDARPP32 ratio and dyskinesias was significant but not strong, pointing to the involvement of convergent factors and signalling pathways. Our results suggest that in dyskinetic rats DRD3 striatal over-expression could be instrumental in the activation of DRD1-downstream signalling and demonstrate that the anti-dyskinetic effect of buspirone in this model is correlated with DRD1 pathway normalization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Morphometry of the ruminal mucosa of Santa Ines lambs fed with levels of palm kernel cake (Elaeis guineensis, from biodiesel productionMorfometria da mucosa ruminal de cordeiros Santa Inês alimentados com níveis de torta de dendê (Elaeis guineensis, oriunda da produção do biodiesel

    Directory of Open Access Journals (Sweden)

    Adriana Regina Bagaldo

    2011-08-01

    Full Text Available The work was carried out to determine the best level of inclusion of palm kernel cake in the concentrate-based morphometry evaluation of the ruminal mucosa in Santa Ines lambs. The experiment lasted 80 days, the Tifton-85 hay in a proportion 50 forage 50concentrado. The food was offered at 9:00 and 16:00. We used 32 sheep of Santa Ines, between 4 and 6 months and body weight of 22 ± 2.75 kg. The experiment was a completely randomized design with four treatments and eight repetitions. The treatments consisted in the inclusion levels of palm kernel cake (0.0, 6.5, 13.0 and 19.5% in the dry matter. Variables evaluated in the ruminal mucosa were: height, width, area, density and thickness of papillary muscular layer of the rumen in the regions of the dorsal and ventral sac. There were no significant differences in the region of the dorsal sac of the rumen for variables analyzed with the inclusion of palm kernel cake in the diet. The ventral surface papillary bag quadratic effect, whereas the thickness of muscular layer decreasing linear effect. The inclusion of up to 19.5% palm kernel cake had no significant effect on the morphology of the papillae may be included in the diet of Santa Ines lambs.O trabalho foi realizado com o objetivo de determinar o melhor nível de inclusão da torta de dendê no concentrado com base na avaliação da morfometria da mucosa ruminal em cordeiros Santa Inês. O período experimental foi de 80 dias, sendo o feno de tifton-85 utilizado na proporção 50 volumoso:50concentrado. O alimento foi ofertado às 9h00 e 16h00. Foram empregados 32 ovinos da raça Santa Inês, entre 4 e 6 meses e peso corporal de 22 ± 2,75kg. O delineamento experimental foi o inteiramente casualizado, com quatro tratamentos e oito repetições. Os tratamentos constituíram-se nos níveis de inclusão da torta de dendê (0,0; 6,5; 13,0 e 19,5 % na matéria seca da ração. As variáveis avaliadas na mucosa ruminal foram: altura, largura, superf

  13. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

    NARCIS (Netherlands)

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with

  14. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease

    NARCIS (Netherlands)

    Antonini, A; Leenders, KL; Vontobel, P; Maguire, RP; Missimer, J; Psylla, M; Gunther, [No Value

    1997-01-01

    We used PET with the tracers [F-18]fluorodeoxyglucose (FDG), [F-18]fluorodopa (FDOPA) and [C-11]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D-2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's

  15. A case of Cotard syndrome: (123)I-IBZM SPECT imaging of striatal D(2) receptor binding.

    Science.gov (United States)

    De Risio, Sergio; De Rossi, Giuseppe; Sarchiapone, Marco; Camardese, Giovanni; Carli, Vladimir; Cuomo, Chiara; Satta, Maria Antonietta; Di Giuda, Daniela

    2004-01-15

    A case of 'dèlire de nègation' that suddenly appeared in a 43-year-old male is presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO-SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2) receptor binding that further decreased after treatment.

  16. Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease.

    Science.gov (United States)

    Ciucci, Michelle R; Schaser, Allison J; Russell, John A

    2013-09-01

    Unilateral lesions to the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) lead to force and timing deficits during a complex licking task. We hypothesized that training targeting tongue force generation during licking would improve timing and force measures and also lead to striatal dopamine sparing. Nine month-old male Fisher344/Brown Norway rats were used in this experiment. Sixteen rats were in the control condition and received tongue exercise (n=8) or no exercise (n=8). Fourteen rats were in the 6-OHDA lesion condition and underwent tongue exercise (n=7) and or no exercise (n=7). Following 4 weeks of training and post-training measures, all animals underwent bilateral stimulation of the hypoglossal nerves to measure muscle contractile properties and were then transcardially perfused and brain tissues collected for immunohistochemistry to examine striatal dopamine content. Results demonstrated that exercise animals performed better for maximal force, average force, and press rate than their no-exercise counterparts, and the 6-OHDA animals that underwent exercise performed as well as the Control No Exercise group. Interestingly, there were no group differences for tetanic muscle force, despite behavioral recovery of forces. Additionally, behavioral and neurochemical analyses indicate that there were no differences in striatal dopamine. Thus, targeted exercise can improve tongue force and timing deficits related to 6-OHDA lesions and this exercise likely has a central, versus peripheral (muscle strength) mechanism. However, this mechanism is not related to sparing of striatal dopamine content. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W. (Brookhaven National Lab., Upton, NY (United States))

    1992-03-01

    An {sup 123}I labeled cocaine analog, 4'-({sup 123}I)iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author).

  18. Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference Learning of State Value in Domestic Chicks

    Directory of Open Access Journals (Sweden)

    Chentao Wen

    2016-11-01

    Full Text Available To ensure survival, animals must update the internal representations of their environment in a trial-and-error fashion. Psychological studies of associative learning and neurophysiological analyses of dopaminergic neurons have suggested that this updating process involves the temporal-difference (TD method in the basal ganglia network. However, the way in which the component variables of the TD method are implemented at the neuronal level is unclear. To investigate the underlying neural mechanisms, we trained domestic chicks to associate color cues with food rewards. We recorded neuronal activities from the medial striatum or tegmentum in a freely behaving condition and examined how reward omission changed neuronal firing. To compare neuronal activities with the signals assumed in the TD method, we simulated the behavioral task in the form of a finite sequence composed of discrete steps of time. The three signals assumed in the simulated task were the prediction signal, the target signal for updating, and the TD-error signal. In both the medial striatum and tegmentum, the majority of recorded neurons were categorized into three types according to their fitness for three models, though these neurons tended to form a continuum spectrum without distinct differences in the firing rate. Specifically, two types of striatal neurons successfully mimicked the target signal and the prediction signal. A linear summation of these two types of striatum neurons was a good fit for the activity of one type of tegmental neurons mimicking the TD-error signal. The present study thus demonstrates that the striatum and tegmentum can convey the signals critically required for the TD method. Based on the theoretical and neurophysiological studies, together with tract-tracing data, we propose a novel model to explain how the convergence of signals represented in the striatum could lead to the computation of TD error in tegmental dopaminergic neurons.

  19. Opiate sensitization induces FosB/ΔFosB expression in prefrontal cortical, striatal and amygdala brain regions.

    Directory of Open Access Journals (Sweden)

    Gary B Kaplan

    Full Text Available Sensitization to the effects of drugs of abuse and associated stimuli contributes to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate exposure produces behavioral sensitization that is hypothesized to result from neural plasticity in specific limbic, striatal and cortical systems. ΔFosB and FosB are members of the Fos family of transcription factors that are implicated in neural plasticity in addiction. This study examined the effects of intermittent morphine treatment, associated with motor sensitization, on FosB/ΔFosB levels using quantitative immunohistochemistry. Motor sensitization was tested in C57BL/6 mice that received six intermittent pre-treatments (on days 1, 3, 5, 8, 10, 12 with either subcutaneous morphine (10 mg/kg or saline followed by a challenge injection of morphine or saline on day 16. Mice receiving repeated morphine injections demonstrated significant increases in locomotor activity on days 8, 10, and 12 of treatment (vs. day 1, consistent with development of locomotor sensitization. A morphine challenge on day 16 significantly increased locomotor activity of saline pre-treated mice and produced even larger increases in motor activity in the morphine pre-treated mice, consistent with the expression of opiate sensitization. Intermittent morphine pre-treatment on these six pre-treatment days produced a significant induction of FosB/ΔFosB, measured on day 16, in multiple brain regions including prelimbic (PL and infralimbic (IL cortex, nucleus accumbens (NAc core, dorsomedial caudate-putamen (CPU, basolateral amygdala (BLA and central nucleus of the amygdala (CNA but not in a motor cortex control region. Opiate induced sensitization may develop via Fos/ΔFosB plasticity in motivational pathways (NAc, motor outputs (CPU, and associative learning (PL, IL, BLA and stress pathways (CNA.

  20. A Framework for Understanding the Emerging Role of Corticolimbic-Ventral Striatal Networks in OCD-Associated Repetitive Behaviors.

    Science.gov (United States)

    Wood, Jesse; Ahmari, Susanne E

    2015-01-01

    Significant interest in the mechanistic underpinnings of obsessive-compulsive disorder (OCD) has fueled research on the neural origins of compulsive behaviors. Converging clinical and preclinical evidence suggests that abnormal repetitive behaviors are driven by dysfunction in cortico-striatal-thalamic-cortical (CSTC) circuits. These findings suggest that compulsive behaviors arise, in part, from aberrant communication between lateral orbitofrontal cortex (OFC) and dorsal striatum. An important body of work focused on the role of this network in OCD has been instrumental to progress in the field. Disease models focused primarily on these regions, however, fail to capture an important aspect of the disorder: affective dysregulation. High levels of anxiety are extremely prevalent in OCD, as is comorbidity with major depressive disorder. Furthermore, deficits in processing rewards and abnormalities in processing emotional stimuli are suggestive of aberrant encoding of affective information. Accordingly, OCD can be partially characterized as a disease in which behavioral selection is corrupted by exaggerated or dysregulated emotional states. This suggests that the networks producing OCD symptoms likely expand beyond traditional lateral OFC and dorsal striatum circuit models, and highlights the need to cast a wider net in our investigation of the circuits involved in generating and sustaining OCD symptoms. Here, we address the emerging role of medial OFC, amygdala, and ventral tegmental area projections to the ventral striatum (VS) in OCD pathophysiology. The VS receives strong innervation from these affect and reward processing regions, and is therefore poised to integrate information crucial to the generation of compulsive behaviors. Though it complements functions of dorsal striatum and lateral OFC, this corticolimbic-VS network is less commonly explored as a potential source of the pathology underlying OCD. In this review, we discuss this network's potential role as

  1. Striatal pre- and postsynaptic profile of adenosine A(2A receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Marco Orru

    2011-01-01

    Full Text Available Striatal adenosine A(2A receptors (A(2ARs are highly expressed in medium spiny neurons (MSNs of the indirect efferent pathway, where they heteromerize with dopamine D(2 receptors (D(2Rs. A(2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1 receptors (A(1Rs. It has been hypothesized that postsynaptic A(2AR antagonists should be useful in Parkinson's disease, while presynaptic A(2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261 showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2AR-D(2R and A(1R-A(2AR heteromers to determine possible differences in the affinity of these compounds for different A(2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2AR when co-expressed with D(2R than with A(1R. KW-6002 showed the best relative affinity for A(2AR co-expressed with D(2R than co-expressed with A(1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile

  2. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-01-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  3. Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

    Science.gov (United States)

    London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

    2018-04-04

    The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

  4. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  5. Análise da dose do laser de baixa potência em equipamentos nacionais Analysis of low-level laser therapy doses in Brazilian equipment

    Directory of Open Access Journals (Sweden)

    TY Fukuda

    2008-02-01

    Full Text Available CONTEXTUALIZAÇÃO: A laserterapia de baixa potência vem sendo cada vez mais utilizada, e o crescente interesse por seus efeitos relaciona-se com a grande quantidade de publicações científicas. Muitos terapeutas e pesquisadores têm-se baseado na definição da dose do laser pela densidade energética (deltaE; porém, a grande variedade de equipamentos de laser pode levar a diferença nos resultados terapêuticos encontrados, por fornecerem parâmetros que variam de acordo com o fabricante. OBJETIVO: Analisar a energia final transmitida ao tecido ao aplicar-se a mesma deltaE em equipamentos de diferentes marcas nacionais. MATERIAIS E MÉTODOS: Foram avaliados sete equipamentos nacionais, com potência média (Pm diferentes, e foram realizadas simulações aplicando deltaE de 1J/cm² em cada aparelho, para avaliar possíveis diferenças na energia final. RESULTADOS: A mesmadeltaE aplicada em diferentes aparelhos nacionais forneceu energia final que variou entre 10 e 90mJ. Esta variação na energia deveu-se principalmente a diferenças na Pm, sendo encontrados valores entre 5,4 e 75mW. CONCLUSÃO: Esta variabilidade na energia final, que é transmitida ao tecido, indica que a deltaE parece não ser o parâmetro que melhor descreve a dose a ser utilizada. É preciso mencionar não só a deltaE, mas também a energia final, para que se possa estabelecer a dose para obtenção do melhor resultado terapêutico.INTRODUCTION: Low-level laser therapy is becoming more popular and there is a growing interest in its effects, as reflected in the increased number of articles published about the subject. Many therapists and researchers have used a laser dose definition based on energy density (deltaE. However, the variety of laser equipments may lead to differences in the therapeutic results found, since the parameters supplied by these equipments vary according to the manufacturer. OBJECTIVE: To analyze the final energy transmitted to the tissue when

  6. Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons.

    Science.gov (United States)

    Winland, Carissa D; Welsh, Nora; Sepulveda-Rodriguez, Alberto; Vicini, Stefano; Maguire-Zeiss, Kathleen A

    2017-11-01

    Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca 2+ ] i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca 2+ ] i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca 2+ ] i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca 2+ ] i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus and a non-vocal learner bird (Colinus virginianus

    Directory of Open Access Journals (Sweden)

    Elena eGarcia-Calero

    2013-12-01

    Full Text Available Striatal projecting neurons, known as medium spiny neurons (MSNs, segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+ MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird: the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order and the non-vocal learner bird quail (representative of galliformes order. We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail, but also between close vocal learner bird families.

  8. Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease

    International Nuclear Information System (INIS)

    Spiegel, J.; Fassbender, K.; Dillmann, U.; Hellwig, D.; Samnick, S.; Moellers, M.-O.; Kirsch, C.-M.; Jost, W.

    2007-01-01

    In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I- 123 ]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p 0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor. (author)

  9. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior.

    Science.gov (United States)

    O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry; Calakos, Nicole

    2017-09-05

    Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

  10. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    DEFF Research Database (Denmark)

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  11. Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington's disease.

    Science.gov (United States)

    Buren, Caodu; Parsons, Matthew P; Smith-Dijak, Amy; Raymond, Lynn A

    2016-03-01

    Huntington's disease (HD) is a genetically inherited neurodegenerative disease caused by a mutation in the gene encoding the huntingtin protein. This mutation results in progressive cell death that is particularly striking in the striatum. Recent evidence indicates that early HD is initially a disease of the synapse, in which subtle alterations in synaptic neurotransmission, particularly at the cortico-striatal (C-S) synapse, can be detected well in advance of cell death. Here, we used a cell culture model in which striatal neurons are co-cultured with cortical neurons, and monitored the development of C-S connectivity up to 21days in vitro (DIV) in cells cultured from either the YAC128 mouse model of HD or the background strain, FVB/N (wild-type; WT) mice. Our data demonstrate that while C-S connectivity in WT co-cultures develops rapidly and continuously from DIV 7 to 21, YAC128 C-S connectivity shows no significant growth from DIV 14 onward. Morphological and electrophysiological data suggest that a combination of pre- and postsynaptic mechanisms contribute to this effect, including a reduction in both the postsynaptic dendritic arborization and the size and replenishment rate of the presynaptic readily releasable pool of excitatory vesicles. Moreover, a chimeric culture strategy confirmed that the most robust impairment in C-S connectivity was only observed when mutant huntingtin was expressed both pre- and postsynaptically. In all, our data demonstrate a progressive HD synaptic phenotype in this co-culture system that may be exploited as a platform for identifying promising therapeutic strategies to prevent early HD-associated synaptopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Behavioral control by striatal adenosine A2A -dopamine D2 receptor heteromers.

    Science.gov (United States)

    Taura, J; Valle-León, M; Sahlholm, K; Watanabe, M; Van Craenenbroeck, K; Fernández-Dueñas, V; Ferré, S; Ciruela, F

    2018-04-01

    G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (ie, GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A 2A receptors (A 2A R) and dopamine D 2 receptors (D 2 R) predominantly form A 2A R-D 2 R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A 2A R and D 2 R within the frame of such a predominant striatal heteromeric population. First, in order to avoid possible strain-related differences, a new D 2 R-deficient mouse with the same genetic background (CD-1) than the A 2A R knock-out mouse was generated. Locomotor activity, pre-pulse inhibition (PPI) and drug-induced catalepsy were then evaluated in wild-type, A 2A R and D 2 R knock-out mice, with and without the concomitant administration of either the D 2 R agonist sumanirole or the A 2A R antagonist SCH442416. SCH442416-mediated locomotor effects were demonstrated to be dependent on D 2 R signaling. Similarly, a significant dependence on A 2A R signaling was observed for PPI and for haloperidol-induced catalepsy. The results could be explained by the existence of one main population of striatal postsynaptic A 2A R-D 2 R heteromers, which may constitute a relevant target for the treatment of Parkinson's disease and other neuropsychiatric disorders. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  13. Altered effect of dopamine transporter 3'UTR VNTR genotype on prefrontal and striatal function in schizophrenia.

    Science.gov (United States)

    Prata, Diana P; Mechelli, Andrea; Picchioni, Marco M; Fu, Cynthia H Y; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Murray, Robin M; Collier, David A; McGuire, Philip

    2009-11-01

    The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Case-control study. Psychiatric research center. Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia

  14. Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.

    Science.gov (United States)

    Balsters, Joshua H; Mantini, Dante; Wenderoth, Nicole

    2018-04-15

    Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Acúmulo e repartição da matéria seca da planta de pepino tipo conserva sob três doses de nutrientes minerais Dry matter accumulation and distribution of pickling cucumber plants under three mineral nutrient levels

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    Hugo Nicasio Rodríguez Espínola

    2001-06-01

    Full Text Available Determinou-se o efeito de três doses de nutrientes minerais sobre o acúmulo e distribuição da matéria seca da planta de pepino tipo conserva, híbrido Crispina. As plantas foram cultivadas em sacolas plásticas com 4,6kg de substrato composto por uma mistura de 40% de casca de arroz e 60% de solo, no interior de uma estufa de polietileno, na primavera de 1998 e no verão de 1999. Foi empregado um delineamento experimental de blocos casualizados, com três repetições e 15 plantas por parcela. Os tratamentos foram constituídos por três níveis múltiplos de uma dose padrão de nutrientes aplicada para cada planta, contendo N-P-K-Ca e Mg nas quantidades de 0,8-0,12-0,8-0,46-0,086g.pl-1, com 0,33m de solução de micronutrientes e 0,07m de quelato de ferro. Os níveis corresponderam às quantidades de 50%, 100% e 150% da dose padrão, denominados de tratamentos T1, T2 e T3, respectivamente, aplicados semanalmente através da fertirrigação em todas as plantas de uma mesma parcela. Determinou-se a matéria seca dos diferentes órgãos da parte aérea da planta a intervalos semanais. Houve efeito significativo dos tratamentos no acúmulo da matéria seca, nos dois experimentos. A maior fração foi alocada para os frutos, atingindo o valor mais elevado de 0,64 na primavera. Concluiu-se que a distribuição da matéria seca desse material vegetal não é constante, sofrendo interações com as variáveis do ambiente.It was determined the effect of three mineral nutrient levels on dry matter accumulation and distribution of pickling cucumber plants, hybrid Crispina, grown inside a polyethylene greenhouse, in spring 1998 and in summer 1999. Planting was made in bags filled with 4.6kg of a substrate mixture composed by 40% rice husks and 60% soil. A randomized block experimental design was used, with three replications and15 plants per plot. A reference nutrient dose was supplied weekly to each one of the plants, with the following composition

  16. Nível sérico da vitamina A em crianças portadoras de leishmaniose visceral Vitamin A serum level in children with visceral leishmaniasis

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    Kleber Giovanni Luz

    2001-01-01

    Full Text Available A vitamina A tem sido considerada uma vitamina anti-infecciosa e sua deficiência está associada a um maior risco de infecções graves, como ocorre por exemplo no sarampo. Nos países em desenvolvimento a hipovitaminose A é um grave problema de saúde pública. O objetivo deste estudo é quantificar o nível sérico da vitamina A em pacientes pediátricos portadores da leismaniose visceral (LV. Amostras de sangue foram coletadas de 22 crianças portadoras de LV, estocadas em freezer e posteriormente, quantificado o nível de vitamina A usando-se a cromatrografia líquída de alta eficiência, nove irmãos assintomáticos dos pacientes foram usados como controles. A média do nível sérico da vitamina A nos portadores de LV foi de 21,38µg/100ml e no grupo controle foi de 31,39µg/100ml. Entre os pacientes estudados com LV a média do nível sérico de vitamina A encontrado foi significativamente menor, utilizando-se o teste t de Student para um pVitamin A is considered an anti-infectious disease vitamin, and its deficiency is associated with severe infections such as in measles. In developing countries the low concentrations of vitamin A are a public health problem. The aim of this study is to describe serum vitamin A concentrations among children with visceral leishmaniasis (VL. Blood sample was collected from 22 children with VL, and stored in a freezer, 9 siblings, with no clinical signs of the VL patients had their blood collected for a control group. Samples were assayed by high performance liquid chromatography. The median vitamin A concentration in the LV group was 21.38µg/100ml and in the control group it was 31.39µg/100. The mean in the LV was statistically lower than in the control group, using Student's t test, p<0.01.

  17. Crescimento do melão Pele de Sapo, em níveis de salinidade e estágio de desenvolvimento da planta Growth of 'Pele de Sapo' muskmelon under salinity levels and development stage of plant

    Directory of Open Access Journals (Sweden)

    Damiana C. de Medeiros

    2012-06-01

    Full Text Available As áreas de cultivo com intensa evaporação, deficiência em drenagem e uso inadequado de fertilizantes, têm aumentado os problemas com a salinidade, prejudicando o rendimento das culturas. O experimento foi conduzido com o objetivo de se avaliar a alocação de massa seca do meloeiro, em função dos diferentes níveis de salinidade da água de irrigação e estágios de desenvolvimento da planta, em Mossoró, RN. O delineamento experimental utilizado foi o de blocos ao acaso, em parcelas subdivididas apresentando, nas parcelas, cinco níveis de salinidade da água de irrigação (0,54, 1,48, 2,02, 3,03 e 3,90 dS m-1 e, nas subparcelas, quatro épocas de coleta de plantas em função dos estágios de seu desenvolvimento (15, 30, 45 e 60 dias após o transplante - DAT correspondendo às fases de crescimento inicial, floração plena, frutificação plena e anterior ao início da colheita, respectivamente, com quatro repetições. Todos os parâmetros de crescimento avaliados foram afetados pela salinidade da água de irrigação. O efeito da salinidade da água sobre a área foliar específica e a massa seca das folhas, foi variável de acordo com a fase de desenvolvimento das plantas. As variáveis mais afetadas pela salinidade da água de irrigação foram a área foliar e a massa seca de frutos, com redução de 28,9 e 24,6%, respectivamente. O maior acúmulo de massa seca no meloeiro Pele de Sapo ocorreu no período entre 30 e 45 dias após o transplantio.The region of Mossoró, RN, Brazil, underwent increasing problems with soil salinity and melon crop yields, mainly in areas with intense evaporation, deficient drainage and inadequate fertilizer use. With this concern, dry mass accumulation in different muskmelon plant organs was evaluated in a trial combining different irrigation water salinity levels and crop growth stages. The experiment was conducted in completely randomized block design with split plot arrangement, having four

  18. Nível de atividade física e hábitos alimentares de universitários do 3º ao 5º semestres da área da saúde Physical activity level and food intake habits of university students from 3 to 5 semester in the health area

    Directory of Open Access Journals (Sweden)

    Priscilla Marcondelli

    2008-02-01

    Full Text Available OBJETIVO: Este trabalho teve como objetivo verificar o nível de atividade física e os hábitos alimentares de universitários da área de saúde visto serem, no futuro, os disseminadores dessas informações. MÉTODOS: Estudo transversal, realizado em 281 estudantes da área da saúde da Universidade de Brasília. Foram avaliadas variáveis antropométricas, de consumo alimentar e de nível de atividade física. RESULTADOS: Observou-se alto nível de sedentarismo nos estudantes da área de saúde, exceto nos alunos de educação física, que praticam atividade física como parte da própria grade curricular. Verificou-se tendência de menor nível de atividade física nos estudantes de menor estrato socioeconômico. A alimentação foi considerada inadequada para a maioria dos estudantes (79,7%. Os menores percentuais relativos a uma alimentação adequada foram observados para o grupo de leite e derivados (23,0%, frutas e vegetais (24,9% e carboidratos complexos (25,9%. Verificou-se um alto percentual de consumo inadequado de refrigerantes e doces (74,0%. O sexo foi associado significantemente ao índice de massa corporal, tendo os homens um índice de massa corporal maior que o das mulheres (pOBJECTIVE: The aim of this work is to assess the physical activity level and nutrition habits of university students from the health area, as they will be future disseminators of such information to the community. METHODS: This was a cross-sectional study with 281 students from the health area from the Universidade de Brasília. Anthropometric variables were evaluated, as well as food habits and physical activity level. RESULTS: A high level of inactivity was observed among the students, except for those of Physical Education who perform physical activities in their school. Low physical activity level was observed among students of low socioeconomic level. Nutrition was considered inadequate for the majority of the students (79.7%. The lowest levels

  19. Resposta da cana-de-açúcar, primeira soca, a níveis de irrigação e adubação de cobertura Response of sugarcane, second leaf, to irrigation levels and topdressing manuring

    Directory of Open Access Journals (Sweden)

    José Dantas Neto

    2006-06-01

    Full Text Available Esta pesquisa foi realizada na Fazenda Capim da Destilaria Miriri, situada no município de Capim na Paraíba, com o objetivo de se identificar o comportamento da cultura da cana-de-açúcar, primeira soca (segunda folha, diante de diferentes lâminas de irrigação e níveis de adubação de cobertura. Com este propósito, conduziu-se um experimento utilizando-se a variedade SP79-1011, em blocos casualizados num arranjo fatorial de 4 x 2 (quatro lâminas de irrigação e dois níveis de adubação de cobertura, com três repetições. O total de água aplicada nos respectivos tratamentos foi 807, 986, 1164 e 1343 mm e os níveis de adubação de cobertura utilizados foram 85 e 305 kg ha-1 da mistura, contendo N e K2O na proporção 1 para 0,94, respectivamente. Analisaram-se parâmetros de crescimento, qualidade e rendimento da cana-de-açúcar. As irrigações influenciaram na fase inicial de crescimento e no início do máximo desenvolvimento da primeira soca. A dose de adubação influenciou mais nos parâmetros analisados que a lâmina de irrigação. A lâmina de irrigação influenciou significativamente, segundo um comportamento linear positivo, os parâmetros de crescimento, enquanto a sacarose (POL da cana apresentou comportamento quadrático.This research was accomplished in the Capim Farm of the Distillery Miriri located in the municipality of Capim city in Paraíba state, Brazil, with the objective of identifying the behavior of sugarcane crop, second leaf, for different irrigation water depths and levels of topdressing manuring with a mixture containing N and K2O in 1:0.94 proportion. With this purpose, an experiment was conducted using the variety SP79-1011, in completely randomized blocks in a factorial scheme of 4 x 2 (four irrigation depths and two levels of topdressing manuring, with three replications. The total water applied in the respective treatments was 807, 986, 1164 and 1343 mm and the levels of topdressing manuring

  20. Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels.

    Science.gov (United States)

    Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M; Sherwin, Robert S; Potenza, Marc N

    2013-02-01

    Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.

  1. Return of reproductive cyclic activity in Morada Nova sheep at metabolizable energy different levels Retorno da atividade cíclica reprodutiva em ovelhas da raça Morada Nova submetidas a diferentes níveis de energia metabolizável

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    Maria Teresa Jansem de Almeida Catanho

    2008-09-01

    Full Text Available The objective, in this work, was to evaluate the effect of metabolizable energy offered on reproductive cyclic activity return of Morada Nova sheep, at different energy levels, during the lactation, since the pregnancy last third, 39 sheep, distributed in three treatments, during the rainy and dry season, were used. Experimental diets were formulated to meet a daily intake of 2.2, 2.8 and 3.4 Mcal of Metabolizable Energy (ME/day and 150 g of crude protein, and the serum levels of progesterone and cortisol regarding, besides the reproductive performance, were evaluated. An entirely casualized design was used in a subdivided scheme for the hormone, and generalized linear models, by the Poisson distribution and binomial distribution in the non-parametric data. There was effect from interaction between period and treatment (P<0,05 for cortisol and progesterone serum, as well as for reproductive performance. The animals went through stress condition, which interfered in the return of reproductive cyclic activity and extended the anoestrus post-partum period, during the dry season. The offer of ME 3.4 Mcal must be recommended for Morada Nova sheep since the pregnancy last third because of the best performance rates and reproductive performance.Este trabalho foi realizado com o objetivo de avaliar os efeitos da energia metabolizável ofertada sobre o retorno da atividade cíclica reprodutiva de ovelhas da raça Morada Nova, durante a lactação, que receberam diferentes níveis de energia desde o terço final da gestação. Foram utilizadas 39 ovelhas distribuídas em três tratamentos durante a época chuvosa e seca. As dietas experimentais foram formuladas para atender ingestão diária de 2,2; 2,8; e 3,4 Mcal de Energia Metabolizável (EM/dia e 150g de proteína bruta, sendo avaliados os níveis séricos de progesterona e cortisol, além do desempenho reprodutivo. Utilizou-se um delineamento inteiramente casualizado, num esquema de parcelas

  2. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    OpenAIRE

    Garcia, Bonnie G.; Neely, M. Diana; Deutch, Ariel Y.

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if dec...

  3. Análise discriminante dos solos por meio da resposta espectral no nível terrestre Soil discrimination analysis by spectral response in the ground level

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    Marcos Rafael Nanni

    2004-10-01

    Full Text Available O objetivo deste trabalho foi desenvolver e avaliar um método para discriminação das classes de solos a partir de suas respostas espectrais, utilizando-se um sensor em laboratório. Os dados espectrais foram utilizados no desenvolvimento de modelos estatísticos para discriminar as classes de solos de uma área no sudoeste do Estado de São Paulo. Equações discriminantes foram desenvolvidas para as 18 classes. A resposta espectral foi obtida em amostras da porção superficial e da porção subsuperficial dos solos da área de estudo, num total de 370 amostras. As amostras foram coletadas em 185 ha, com uma tradagem por ha. Os resultados demonstraram que as classes de solos podem ser individualizadas e distinguidas pela análise discriminante. A análise registrou índices de acerto acima de 80% de determinação da classe de solo avaliada. O acerto global foi de 90,71% quando se utilizaram todas as classes para a geração dos modelos, e 93,44% quando se utilizaram as dez classes com maior número de indivíduos. O teste estatístico simulado mostrou-se eficiente na análise discriminante, com taxa média de acerto acima de 91%, com erro global de 8,8%. A análise demonstrou redução na qualidade do modelo quando aplicado para um subconjunto de 20% das amostras, com erro global de 33,9%. O método auxilia na discriminação de classes de solos pela sua reflectância, devido às interações físicas com a energia eletromagnética.The objective of this study was to develop and test a discrimination method for soil classes by their spectral response (SR, using a laboratory sensor. Spectral data were used to develop statistical model for discriminating soil classes in an area at the southwest of São Paulo State, Brazil. Discriminant equations were developed for 18 soil classes. The spectral data were obtained in superficial and subsuperficial soil samples in the study area, with a total of 370 samples. The samples were collected in 185 ha

  4. Influência da resposta inflamatória de fase aguda nos níveis séricos de retinol e da proteína de ligação do retinol em pacientes com AIDS Influence of acute-phase inflammatory response on serum levels of retinol and retinol binding protein in HIV/AIDS patients

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    Fábio Fernandes Neves

    2010-02-01

    Full Text Available INTRODUÇÃO: a hiporretinolemia constitui fator prognóstico independente em pacientes com AIDS, e a atividade inflamatória causa redução dos níveis séricos deste nutriente na população em geral. Entretanto, faltam estudos que avaliem o impacto da atividade inflamatória sobre o nível sérico do retinol em pacientes com AIDS. MÉTODOS: foram avaliados transversalmente 41 pacientes internados por complicações da AIDS, que tiveram quantificados alguns marcadores de inflamação (proteína C reativa e fator de necrose tumoral alfa e concentrações séricas de retinol e da proteína de ligação do retinol. RESULTADOS: apesar da baixa (14,6% prevalência de hiporretinolemia evidenciou-se correlação negativa dos marcadores de inflamação com os níveis séricos de retinol e de sua proteína de ligação nos pacientes com AIDS. CONCLUSÕES: a atividade inflamatória de fase aguda está associada a baixos níveis séricos de retinol em indivíduos com AIDS.INTRODUCTION: Hyporetinolemia is an independent prognostic factor in AIDS patients. Inflammatory activity causes a reduction in the serum levels of this nutrient in the general population. However, there are no studies assessing the impact of inflammatory activity on the serum retinol level in AIDS patients. METHODS: A cross-sectional assessment was conducted on 41 patients hospitalized due to AIDS complications. Inflammatory markers (C-reactive protein and tumor necrosis factor-alpha and serum retinol and retinol binding protein concentrations were quantified. RESULTS: Despite the low (14.6% prevalence of hyporetinolemia, a significant negative correlation was observed between the inflammatory markers and the serum retinol and retinol binding protein levels in AIDS patients. CONCLUSIONS: Acute-phase inflammatory activity is associated with low serum retinol levels in individuals with AIDS.

  5. The impact of reconstruction method on the quantification of DaTSCAN images

    Energy Technology Data Exchange (ETDEWEB)

    Dickson, John C.; Erlandsson, Kjell; Hutton, Brian F. [UCLH NHS Foundation Trust and University College London, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [Southampton University Hospitals NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Varrone, Andrea [Psychiatry Section and Stockholm Brain Institute, Karolinska Institute, Department of Clinical Neuroscience, Stockholm (Sweden); Tatsch, Klaus [EANM/European Network of Excellence for Brain Imaging, Vienna (Austria)

    2010-01-15

    Reconstruction of DaTSCAN brain studies using OS-EM iterative reconstruction offers better image quality and more accurate quantification than filtered back-projection. However, reconstruction must proceed for a sufficient number of iterations to achieve stable and accurate data. This study assessed the impact of the number of iterations on the image quantification, comparing the results of the iterative reconstruction with filtered back-projection data. A striatal phantom filled with {sup 123}I using striatal to background ratios between 2:1 and 10:1 was imaged on five different gamma camera systems. Data from each system were reconstructed using OS-EM (which included depth-independent resolution recovery) with various combinations of iterations and subsets to achieve up to 200 EM-equivalent iterations and with filtered back-projection. Using volume of interest analysis, the relationships between image reconstruction strategy and quantification of striatal uptake were assessed. For phantom filling ratios of 5:1 or less, significant convergence of measured ratios occurred close to 100 EM-equivalent iterations, whereas for higher filling ratios, measured uptake ratios did not display a convergence pattern. Assessment of the count concentrations used to derive the measured uptake ratio showed that nonconvergence of low background count concentrations caused peaking in higher measured uptake ratios. Compared to filtered back-projection, OS-EM displayed larger uptake ratios because of the resolution recovery applied in the iterative algorithm. The number of EM-equivalent iterations used in OS-EM reconstruction influences the quantification of DaTSCAN studies because of incomplete convergence and possible bias in areas of low activity due to the nonnegativity constraint in OS-EM reconstruction. Nevertheless, OS-EM using 100 EM-equivalent iterations provides the best linear discriminatory measure to quantify the uptake in DaTSCAN studies. (orig.)

  6. Desigualdades sócio-espaciais da adequação das informações de nascimentos e óbitos do Ministério da Saúde, Brasil, 2000-2002 Socio-spatial inequalities in the adequacy of Ministry of Health data on births and deaths at the municipal level in Brazil, 2000-2002

    Directory of Open Access Journals (Sweden)

    Carla Lourenço Tavares de Andrade

    2007-05-01

    Full Text Available Neste trabalho, analisam-se as desigualdades sócio-espaciais da adequação das informações de nascimentos (SINASC e óbitos (SIM do Ministério da Saúde para o cálculo da mortalidade infantil por município. A análise foi realizada de acordo com o porte populacional do município e região geográfica no período 2000-2002, considerando-se cinco indicadores: coeficiente geral de mortalidade padronizado por idade; razão entre nascidos vivos informados e estimados; desvio médio relativo do coeficiente de mortalidade; desvio médio relativo da taxa de natalidade; percentual de óbitos sem definição da causa básica de morte. Os critérios de adequação foram estabelecidos estatisticamente nas Unidades da Federação com informações consideradas adequadas. Os resultados mostram desigualdades sócio-espaciais importantes: o percentual de adequação é maior no Centro-Sul e entre os municípios de maior porte populacional. Em relação aos três aspectos estudados, o SINASC teve a melhor avaliação. Quanto ao SIM, além de reduzir a subnotificação, é preciso melhorar a qualidade do preenchimento da causa de óbito, para que as informações possam orientar adequadamente os programas de saúde voltados para a redução das iniqüidades da mortalidade infantil no Brasil.This study analyzed socio-spatial inequalities in the adequacy of Ministry of Health data systems on live births (SINASC and deaths (SIM for estimating infant mortality at the municipal level in Brazil. Data from 2000-2002 for all municipalities were analyzed according to population size and geographic region. Five indicators were considered: age-standardized mortality rate; ratio of reported-to-estimated live births; relative mean deviation of the mortality rate; relative mean deviation of the birth rate; and proportion of deaths with undetermined causes. Adequacy criteria were established statistically for eight Brazilian States in which vital statistics were

  7. Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake

    Science.gov (United States)

    Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Weng, Yi-Hsin

    2015-01-01

    Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [99mTc]-TRODAT with SPECT imaging. Procedures. A normal [99mTc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R 2 = 0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients. PMID:26366413

  8. Fully Automated Quantification of the Striatal Uptake Ratio of [(99m)Tc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake.

    Science.gov (United States)

    Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Yen, Tzu-Chen; Weng, Yi-Hsin

    2015-01-01

    We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [(99m)Tc]-TRODAT with SPECT imaging. A normal [(99m)Tc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R (2) = 0.84. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

  9. Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson’s Disease and the Temporal Regression of Striatal Tracer Uptake

    Directory of Open Access Journals (Sweden)

    Yu-Hua Dean Fang

    2015-01-01

    Full Text Available Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging. Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365 and nPD subjects (28 healthy controls and 33 essential tremor patients were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR. The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R2=0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

  10. Selective increase of auditory cortico-striatal coherence during auditory-cued Go/NoGo discrimination learning.

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    Andreas L. Schulz

    2016-01-01

    Full Text Available Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcementmodels, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functionalcoupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed.

  11. In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography

    International Nuclear Information System (INIS)

    Aquilonius, S.-M.; Bergstroem, K.; Eckernaes, S.-Aa.; Leenders, K.L.; Hartvig, P.; Lundquist, H.; Antoni, G.; Gee, A.; Rimland, A.; Uhlin, J.; Langstroem, B.

    1987-01-01

    In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11 C-nomifensine was administered i.v. in trace amounts (10-50 μg) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the timecourse of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11 C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11 C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11 C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11 C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11 C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11 C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo. (author)

  12. [18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease.

    Science.gov (United States)

    Stark, Adam J; Smith, Christopher T; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Donahue, Manus J; Kessler, Robert M; Deutch, Ariel Y; Zald, David H; Claassen, Daniel O

    2018-01-01

    Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18 F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

  13. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    Science.gov (United States)

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  14. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    Science.gov (United States)

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

  15. Efeito da duração da amamentação exclusiva e mista sobre os níveis de hemoglobina nos primeiros seis meses de vida: um estudo de seguimento Effect of length of exclusive breastfeeding and mixed feeding on hemoglobin levels in the first six months of life: a follow-up study

    Directory of Open Access Journals (Sweden)

    Andréa Silva de Oliveira

    2010-02-01

    Full Text Available O objetivo deste estudo foi avaliar o efeito da duração da amamentação exclusiva e mista sobre os níveis de hemoglobina de lactentes. Trata-se de um estudo de seguimento com seis meses de duração, envolvendo 150 crianças nascidas na maternidade de Mutuípe, Bahia, Brasil. Mensalmente, as crianças eram submetidas ao exame de sangue para avaliação dos níveis de hemoglobina e realizava-se coleta de dados de consumo alimentar. Foram obtidos, ainda, dados obstétricos e sócio-econômicos. Utilizou-se o modelo linear de efeitos mistos para investigar as associações de interesse. Ao final do seguimento, a perda amostral foi de 15,3%, e detectou-se uma prevalência de 71,7% de anemia. Constatou-se um incremento de 0,091g/dL nos níveis de hemoglobina a cada mês de duração de aleitamento materno exclusivo (p = 0,031, enquanto, a cada mês de duração de aleitamento materno misto, os níveis de hemoglobina declinaram em 0,097g/dL (p = 0,017. Concluiu-se que as práticas alimentares inadequadas parecem estar diretamente envolvidas na etiologia da deficiência nutricional de ferro nesse período da vida.This six-month follow-up study aimed to assessing the effect of length of both exclusive breastfeeding and mixed feeding on hemoglobin levels in 150 infants born at the Mutuípe maternity facility in Bahia State, Brazil. Blood tests were performed monthly to assess the hemoglobin levels, at which time data were gathered on food intake. Obstetric and socioeconomic data were also collected. The linear mixed effects model was used to investigate the target associations. Loss to follow-up was 15.3%, and anemia prevalence was 71.7%. An increase of 0.091g/dL (p = 0.031 in hemoglobin levels was found for each month of exclusive breastfeeding, while a decrease of 0.097g/dL (p = 0.017 was shown for each month of mixed feeding. In conclusion, inadequate food practices appear to be directly involved in the etiology of iron deficiency anemia during

  16. Produtividade da biomassa de melissa em função de intervalo de cortes e doses de nitrogênio Biomass production of Lemon balm as a result of cutting interval and nitrogen levels

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    André May

    2008-09-01

    Full Text Available A espécie Melissa officinalis tem crescido em importância econômica no setor produtivo de plantas medicinais, contudo o nível de informações agronômicas a cerca da espécie é limitado. Dessa forma, foi instalado um experimento visando avaliar a influência do intervalo de cortes e de doses de nitrogênio sobre a produção de biomassa dessa espécie. O delineamento experimental utilizado foi o de blocos ao acaso, com três repetições, em esquema fatorial 4 x 4, sendo os fatores estudados o intervalo de cortes (30; 42; 54 e 66 dias e dose de nitrogênio (0; 60; 120 e 180 kg ha-1 de N. Foram avaliadas a altura da planta e massa seca da parte aérea. Observou-se maior altura da planta para maior intervalo entre corte. Maiores rendimentos de massa seca foram observados com a aplicação de 180 kg ha-1 de N, havendo uma resposta linear para a produção de massa seca com a aplicação de N.Cultivation of Melissa officinalis is increasing in economic importance in the market of medicinal plants, although the level of agronomic information concerning the specie is limited. To achieve those objectives, a trial was carried out to study the influence of cutting intervals and nitrogen levels in biomass production. The experimental design was in blocks with three replications in a 4 x 4 factorial cheme: cutting intervals (30; 42; 54 and 66 days and nitrogen (0; 60; 120 and 180 kg ha-1 of N. The characteristics of plant height and aerial part and accumulated dry mater were evaluated. Increasing the cutting intervals resulted in higher plants. The highest dry matter value was observed using 180 kg ha-1 of N, having a linear reply for the production of dry mass with the application of N.

  17. Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

    Science.gov (United States)

    Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

    2013-06-01

    Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Exploring personality traits related to dopamine D2/3 receptor availability in striatal subregions of humans.

    Science.gov (United States)

    Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

    2016-04-01

    While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  19. Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration

    Science.gov (United States)

    Bhalla, Upinder S.; Hellgren Kotaleski, Jeanette

    2016-01-01

    In reward learning, the integration of NMDA-dependent calcium and dopamine by striatal projection neurons leads to potentiation of corticostriatal synapses through CaMKII/PP1 signaling. In order to elicit the CaMKII/PP1-dependent response, the calcium and dopamine inputs should arrive in temporal proximity and must follow a specific (dopamine after calcium) order. However, little is known about the cellular mechanism which enforces these temporal constraints on the signal integration. In this computational study, we propose that these temporal requirements emerge as a result of the coordinated signaling via two striatal phosphoproteins, DARPP-32 and ARPP-21. Specifically, DARPP-32-mediated signaling could implement an input-interval dependent gating function, via transient PP1 inhibition, thus enforcing the requirement for temporal proximity. Furthermore, ARPP-21 signaling could impose the additional input-order requirement of calcium and dopamine, due to its Ca2+/calmodulin sequestering property when dopamine arrives first. This highlights the possible role of phosphoproteins in the temporal aspects of striatal signal transduction. PMID:27584878

  20. 6-hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors

    International Nuclear Information System (INIS)

    Porceddu, M.L.; Giorgi, O.; De Montis, G.; Mele, S.; Cocco, L.; Ongini, E.; Biggio, G.

    1987-01-01

    Dopamine-sensitive adenylate cyclase and 3 H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3 H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3 H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3 H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table

  1. Impacto da suplementação com retinil palmitato no pós-parto imediato sobre os níveis de retinol do colostro Impact on colostrum retinol levels of immediate postpartum supplementation with retinyl palmitate

    Directory of Open Access Journals (Sweden)

    Roberto Dimenstein

    2007-07-01

    Full Text Available OBJETIVO: Avaliar o efeito da suplementação com retinil palmitato sobre os níveis de retinol no colostro, investigando a influência de variáveis maternas (idade, tipo de parto e estado nutricional bioquímico sobre esses níveis. MÉTODO:Participaram do estudo 33 nutrizes atendidas na Maternidade Escola Januário Cicco, Estado do Rio Grande do Norte, Brasil. Foram coletadas, nas primeiras horas após o parto, uma amostra de sangue e uma de colostro. Uma nova amostra de colostro foi coletada 6 horas após suplementação materna com 200 000 UI de retinil palmitato. O retinol no sangue e colostro foi determinado por cromatografia líquida de alta eficiência. RESULTADOS: Os níveis médios de retinol no colostro antes da suplementação foram de 110,8 ± 82,3 µg/dL, tendo atingido 164,4 ± 106,5 µg/dL após a suplementação (P OBJECTIVE: To assess the effect of retinyl palmitate supplementation on colostrum retinol levels, investigating the influence of maternal variables (age, type of delivery, and biochemical nutritional status on these levels. METHOD: The study included 33 mothers receiving care at the Januário Cicco Maternity School, in the city of Natal, Rio Grande do Norte, Brazil. In the first hours after delivery, blood and colostrum samples were collected. Another colostrum sample was collected six hours after maternal supplementation with 200 000 IU of retinyl palmitate. Serum and colostrum retinol levels were determined by high-performance liquid chromatography. RESULTS: The mean retinol level in colostrum before the supplementation was 110.8 ± 82.3 µg/dL, and after supplementation it was 164.4 ± 106.5 µg/dL (P < 0.025. Of the 33 mothers, 12 of them either did not respond to supplementation or had an increase of less than 10% in colostrum retinol levels; serum retinol in these women was significantly lower as compared to the responders (P = 0.024. In comparison to women with a normal delivery, the mothers who underwent

  2. Efeito da adição de níveis crescentes de polpa cítrica sobre a qualidade fermentativa e o valor nutritivo da silagem de capim-elefante Effect of increasing levels of citrus pulp on the fermentation quality and nutritive value of elephantgrass silage

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Mazza Rodrigues

    2005-08-01

    Full Text Available Foram estudados os efeitos da adição de polpa cítrica sobre a qualidade fermentativa e o valor nutritivo da silagem de capim-elefante. O capim-elefante, apresentando 90 dias de crescimento, foi ensilado com níveis crescentes de polpa cítrica peletizada: 0; 2,5; 5; 7,5; 10; 12,5 e 15%, com base na matéria fresca. As silagens foram produzidas em 28 silos experimentais (quatro repetições/tratamento, confeccionados a partir de baldes plásticos com válvulas do tipo Bunsen. A abertura dos silos ocorreu 106 dias após a ensilagem, quando foram determinados os teores dos ácidos orgânicos e a composição químico-bromatológica das silagens. Foi observado efeito linear crescente da adição de polpa cítrica sobre os teores de matéria seca, o mesmo ocorrendo para carboidratos solúveis e digestibilidade in vitro da matéria seca, mas com redução nos teores de nitrogênio amoniacal e fibra em detergente neutro. Para os teores de ácidos orgânicos (acético, lático e butírico e etanol, observou-se comportamento quadrático para as curvas obtidas, com pontos de máxima para o ácido lático igual a 5,8% e de mínima para os ácidos acético, butírico e o etanol, iguais a 7,8; 7,2; e -3,7% de polpa, respectivamente. Não foram observados efeitos sobre os valores de pH, assim como para os teores de lignina e de ácido propiônico. Inclusões de 4,7 a 7,6% de polpa cítrica peletizada, com base na matéria fresca, são suficientes para melhorar a qualidade e o valor nutritivo da silagem de capim-elefante.The effects of increasing levels of citrus pulp on fermentation pattern and nutritive value of elephantgrass silage was evaluated. Elephantgrass harvested at 90 days was ensiled with increasing levels of dried citrus pulp: 0, 2.5, 5, 7.5, 10, 12.5 and 15% (fresh matter basis. Silages were produced in 28 plastic experimental silos (4 replicates/treatment bearing Bunsen valves. Silos were opened 106 days after ensiling, when samples were

  3. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

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    Marina ePolito

    2013-11-01

    Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

  4. A neurobehavioral examination of individuals with high-functioning autism and Asperger's disorder using a fronto-striatal model of dysfunction.

    Science.gov (United States)

    Rinehart, Nicole J; Bradshaw, John L; Tonge, Bruce J; Brereton, Avril V; Bellgrove, Mark A

    2002-06-01

    The repetitive, stereotyped, and obsessive behaviors that characterize autism may in part be attributable to disruption of the region of the fronto-striatal system, which mediates executive abilities. Neuropsychological testing has shown that children with autism exhibit set-shifting deficiencies on tests such as the Wisconsin Card Sorting task but show normal inhibitory ability on variants of the Stroop color-word test. According to Minshew and Goldstein's multiple primary deficit theory, the complexity of the executive functioning task is important in determining the performance of individuals with autism. This study employed a visual-spatial task (with a Stroop-type component) to examine the integrity of executive functioning, in particular inhibition, in autism (n = 12) and Asperger's disorder (n = 12) under increasing levels of cognitive complexity. Whereas the Asperger's disorder group performed similarly to age- and IQ-matched control participants, even at the higher levels of cognitive complexity, the high-functioning autism group displayed inhibitory deficits specifically associated with increasing cognitive load.

  5. Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

    Science.gov (United States)

    Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

    2017-05-01

    According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

  6. Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats.

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    Ting Wu

    Full Text Available Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.

  7. Striatal-enriched Tyrosine Protein Phosphatase (STEP) in the Mechanisms of Depressive Disorders.

    Science.gov (United States)

    Kulikova, Elizabeth; Kulikov, Alexander

    2017-08-30

    Striatal-enriched tyrosine protein phosphatase (STEP) is expressed mainly in the brain. Its dysregulation is associated with Alzheimer's and Huntington's diseases, schizophrenia, fragile X syndrome, drug abuse and stroke/ischemia. However, an association between STEP and depressive disorders is still obscure. The review discusses the theoretical foundations and experimental facts concerning possible relationship between STEP dysregulation and depression risk. STEP dephosphorylates and inactivates several key neuronal signaling proteins such as extracellular signal-regulating kinase 1 and 2 (ERK1/2), stress activated protein kinases p38, the Src family tyrosine kinases Fyn, Pyk2, NMDA and AMPA glutamate receptors. The inactivation of these proteins decreases the expression of brain derived neurotrophic factor (BDNF) necessary for neurogenesis and neuronal survival. The deficit of BDNF results in progressive degeneration of neurons in the hippocampus and cortex and increases depression risk. At the same time, a STEP inhibitor, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), increases BDNF expression in the hippocampus and attenuated the depressivelike behavior in mice. Thus, STEP is involved in the mechanism of depressive disorders and it is a promising molecular target for atypical antidepressant drugs of new generation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Magnetic resonance imaging (MRI to study striatal iron accumulation in a rat model of Parkinson's disease.

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    Ana Virel

    Full Text Available Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI. The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron.

  9. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.

    Science.gov (United States)

    Rothwell, Patrick E; Fuccillo, Marc V; Maxeiner, Stephan; Hayton, Scott J; Gokce, Ozgun; Lim, Byung Kook; Fowler, Stephen C; Malenka, Robert C; Südhof, Thomas C

    2014-07-03

    In humans, neuroligin-3 mutations are associated with autism, whereas in mice, the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse and thereby provide a plausible circuit substrate for autism pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Age differences in striatal delay sensitivity during intertemporal choice in healthy adults

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    Gregory R Samanez-Larkin

    2011-11-01

    Full Text Available Intertemporal choices are a ubiquitous class of decisions that involve selecting between outcomes available at different times in the future. We investigated the neural systems supporting intertemporal decisions in healthy younger and older adults. Using functional neuroimaging, we find that aging is associated with a shift in the brain areas that respond to delayed rewards. Although we replicate findings that brain regions associated with the mesolimbic dopamine system respond preferentially to immediate rewards, we find a separate region in the ventral striatum with very modest time dependence in older adults. Activation in this striatal region was relatively insensitive to delay in older but not younger adults. Since the dopamine system is believed to support associative learning about future rewards over time, our observed transfer of function may be due to greater experience with delayed rewards as people age. Identifying differences in the neural systems underlying these decisions may contribute to a more comprehensive model of age-related change in intertemporal choice.

  11. Familial Risk for Major Depression is Associated with Lower Striatal 5-HT4 Receptor Binding

    DEFF Research Database (Denmark)

    Madsen, Karine; Torstensen, Eva; Holst, Klaus K

    2014-01-01

    was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [(11)C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. METHODS: We studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first......-degree relatives treated for MDD. RESULTS: We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first......-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). CONCLUSIONS: Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression...

  12. The neostriatal mosaic: striatal patch-matrix organization is related to cortical lamination.

    Science.gov (United States)

    Gerfen, C R

    1989-10-20

    The basal ganglia, of which the striatum is the major component, process inputs from virtually all cerebral cortical areas to affect motor, emotional, and cognitive behaviors. Insights into how these seemingly disparate functions may be integrated have emerged from studies that have demonstrated that the mammalian striatum is composed of two compartments arranged as a mosaic, the patches and the matrix, which differ in their neurochemical and neuroanatomical properties. In this study, projections from prefrontal, cingulate, and motor cortical areas to the striatal compartments were examined with the Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde axonal tracer in rats. Each cortical area projects to both the patches and the matrix of the striatum; however, deep layer V and layer VI corticostriatal neurons project principally to the patches, whereas superficial layer V and layer III and II corticostriatal neurons project principally to the matrix. The relative contribution of patch and matrix corticostriatal projections varies among the cortical areas examined such that allocortical areas provide a greater number of inputs to the patches than to the matrix, whereas the reverse obtains for neocortical areas. These results demonstrate that the compartmental organization of corticostriatal inputs is related to their laminar origin and secondarily to the cytoarchitectonic area of origin.

  13. Effect of in vitro inorganic lead on dopamine release from superfused rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Minnema, D.J.; Greenland, R.D.; Michaelson, I.A.

    1986-01-01

    The effect of inorganic lead in vitro in several aspects of [ 3 H]dopamine release from superfused rat striatal synaptosomes was examined. Under conditions of spontaneous release, lead (1-30 microM) induced dopamine release in a concentration-dependent manner. The onset of the lead-induced release was delayed by approximately 15-30 sec. The magnitude of dopamine release induced by lead was increased when calcium was removed from the superfusing buffer. Lead-induced release was unaffected in the presence of putative calcium, sodium, and/or potassium channel blockers (nickel, tetrodotoxin, tetraethylammonium, respectively). Depolarization-evoked dopamine release, produced by a 1-sec exposure to 61 mM potassium, was diminished at calcium concentrations below 0.254 mM. The onset of depolarization-evoked release was essentially immediate following exposure of the synaptosomes to high potassium. The combination of lead (3 or 10 microM) with high potassium reduced the magnitude of depolarization-evoked dopamine release. This depression of depolarization-evoked release by lead was greater in the presence of 0.25 mM than 2.54 mM calcium in the superfusing buffer. These findings demonstrate multiple actions of lead on synaptosomal dopamine release. Lead can induce dopamine release by yet unidentified neuronal mechanisms independent of external calcium. Lead can also reduce depolarization-evoked dopamine release by apparent competition with calcium influx at the neuronal membrane calcium channel

  14. Study of the neural basis of striatal modulation of the jaw-opening reflex.

    Science.gov (United States)

    Barceló, Ana C; Fillipini, B; Pazo, Jorge Horacio

    2010-02-01

    Previous experimental data from this laboratory demonstrated the participation of the striatum and dopaminergic pathways in central nociceptive processing. The objective of this study was to examine the possible pathways and neural structures associated with the analgesic action of the striatum. The experiments were carried out in rats anesthetized with urethane. The jaw-opening reflex (JOR) was evoked by electrical stimulation of the tooth pulp of lower incisors and recorded in the anterior belly of the digastric muscles. Intrastriatal microinjection of apomorphine, a nonspecific dopamine agonist, reduced or abolished the JOR amplitude. Electrolytic or kainic acid lesions, unilateral to the apomorphine-injected striatum, of the globus pallidus, substantia nigra pars reticulata, subthalamic nucleus and bilateral lesion the rostroventromedial medulla (RVM), blocked the inhibition of the JOR by striatal stimulation. These findings suggest that the main output nuclei of the striatum and the RVM may be critical elements in the neural pathways mediating the inhibition of the reflex response, evoked in jaw muscles by noxious stimulation of dental pulp.

  15. Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

    Science.gov (United States)

    Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

    2016-08-01

    The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

  16. Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.

    Science.gov (United States)

    Jaramillo, Anel A; Agan, Verda E; Makhijani, Viren H; Pedroza, Stephen; McElligott, Zoe A; Besheer, Joyce

    2017-09-27

    The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control. © 2017 Society for the Study of Addiction.

  17. Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

    Directory of Open Access Journals (Sweden)

    Jovana eBelic

    2016-03-01

    Full Text Available We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the healthy state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

  18. The behavior of temperature in photovoltaic panels efficiency at different levels of incidence of solar radiance associated with temperature; O comportamento da temperatura na eficiencia de paineis fotovoltaicos em diferentes niveis de incidencia da radiancia solar associado a temperatura

    Energy Technology Data Exchange (ETDEWEB)

    Michels, Roger N.; Jesus, Manoel M.A.; Tarricone, Georgia [Universidade Tecnologica Federal do Paran (UTFPR), Apucarana, PR (Brazil)], email: rogernmichels@utfpr.edu.br; Gnoatto, Estor; Kavanagh, Edward [Universidade Tecnologica Federal do Paran (UTFPR), Medianeira, PR (Brazil)

    2011-07-01

    The efficiency of photovoltaic panels is related to factors of construction of the cell, as well as external factors. One of the external factors, which negatively affects the efficiency of photovoltaic panels, is the temperature. This work analyzes the influence of temperature on the efficiency of photovoltaic panels, with different levels of incidence of solar radiation (500, 700, 900 and 1000 Wm{sup -2}). The photovoltaic system, composed of photovoltaic panels and a positive displacement pump was installed at the Federal Technological University of Parana in the city of Medianeira. Data were collected during the period of one year, but only data from clear days were used, which did not occur to the influence of shading of clouds on the values obtained. Observed in this work, the temperature increase in photovoltaic panels, makes the efficiency decreases due to the decrease of voltage and power. (author)

  19. Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and adiponectin before and after oral glucose uptake in slim adults

    Directory of Open Access Journals (Sweden)

    Schäffler Andreas

    2007-02-01

    Full Text Available Abstract Background Adipose tissue secreted proteins are collectively named adipocytokines and include leptin, adiponectin, resistin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and omentin. Several of these adipocytokines influence insulin sensitivity and glucose metabolism and therefore systemic levels may be affected by oral glucose uptake. Whereas contradictory results have been published for leptin and adiponectin, resistin has not been extensively investigated and no reports on omentin and CORS-26 do exist. Methods Therefore the plasma levels of these proteins before and 120 min after an oral glucose load were analyzed in 20 highly-insulin sensitive, young adults by ELISA or immunoblot. Results Circulating leptin was reduced 2 h after glucose uptake whereas adiponectin and resistin levels are not changed. Distribution of adiponectin and CORS-26 isoforms were similar before and after glucose ingestion. Omentin is highly abundant in plasma and immunoblot analysis revealed no alterations when plasma levels before and 2 h after glucose intake were compared. Conclusion Taken together our data indicate that only leptin is reduced by glucose uptake in insulin-sensitive probands whereas adiponectin and resistin are not altered. CORS-26 was demonstrated for the first time to circulate as high molecular weight form in plasma and like omentin was not influenced by oral glucose load. Omentin was shown to enhance insulin-stimulated glucose uptake but systemic levels are not correlated to postprandial blood glucose.

  20. Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.

    Science.gov (United States)

    Scarpa, Joseph R; Jiang, Peng; Losic, Bojan; Readhead, Ben; Gao, Vance D; Dudley, Joel T; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2016-07-01

    Recent systems-based analyses have demonstrated that sleep and stress traits emerge from shared genetic and transcriptional networks, and clinical work has elucidated the emergence of sleep dysfunction and stress susceptibility as early symptoms of Huntington's disease. Understanding the biological bases of these early non-motor symptoms may reveal therapeutic targets that prevent disease onset or slow disease progression, but the molecular mechanisms underlying this complex clinical presentation remain largely unknown. In the present work, we specifically examine the relationship between these psychiatric traits and Huntington's disease (HD) by identifying striatal transcriptional networks shared by HD, stress, and sleep phenotypes. First, we utilize a systems-based approach to examine a large publicly available human transcriptomic dataset for HD (GSE3790 from GEO) in a novel way. We use weighted gene coexpression network analysis and differential connectivity analyses to identify transcriptional networks dysregulated in HD, and we use an unbiased ranking scheme that leverages both gene- and network-level information to identify a novel astrocyte-specific network as most relevant to HD caudate. We validate this result in an independent HD cohort. Next, we computationally predict FOXO3 as a regulator of this network, and use multiple publicly available in vitro and in vivo experimental datasets to validate that this astrocyte HD network is downstream of a signaling pathway important in adult neurogenesis (TGFβ-FOXO3). We also map this HD-relevant caudate subnetwork to striatal transcriptional networks in a large (n = 100) chronically stressed (B6xA/J)F2 mouse population that has been extensively phenotyped (328 stress- and sleep-related measurements), and we show that this striatal astrocyte network is correlated to sleep and stress traits, many of which are known to be altered in HD cohorts. We identify causal regulators of this network through Bayesian network

  1. O perfil de um grupo de pessoas hipertensas de acordo com conhecimento e gravidade da doença The profile of hypertensive patients related to awareness and level of hypertension

    Directory of Open Access Journals (Sweden)

    Angela M.G. Pierin

    2001-03-01

    Full Text Available Foram entrevistados 205 hipertensos em tratamento ambulatorial para avaliar o papel do perfil bio-social no conhecimento e grau de gravidade da doença. As características da população foram: 72% mulheres, 63% brancos, 78% com mais de 40 anos, 60% casados, 68% com baixa escolaridade, 41% com renda de 1 a 3 salários, 75% com peso elevado, 76% não fumantes, 89% sem atividade física regular, e das mulheres 48% já tinham usado hormônios anticoncepcionais. A análise evidenciou que a ausência de conhecimento se associou com sexo masculino, idade entre 20 e 40 anos, viúvo, não branco e peso normal. Pressão arterial mais elevada (diastólica> 110 mm Hg se associou com mais de 60 anos, não casado, acima do peso, baixa escolaridade, baixa renda, com mais de 5 anos de hipertensão e já ter feito tratamento anterior.We interviewed 205 hypertensives to characterize social demographic data, life style, history and awareness of hypertension. Most patients were female (72%, white (63%, over 40 years old (78%, married (60%, and had low level of education (68%. Their family income was lower than US$ 3000 a year (41%. In terms of weight, 75% were classified as overweight, 76% were non smoker, and 89% did not do any regular physical activity. The profile of the hypertensives who were unaware of the disease was: male, 20-40 years old, widow, not white, and non-obese. The profile of the hypertensives who had high level of hypertension (diastólic> 110 mm Hg was older than 60 years old, not married, overweight, low level of education, low income, with more than 5 years of hypertension, and previously treated.

  2. Seca dos ponteiros da goiabeira causada por Erwinia psidii: níveis de incidência e aspectos epidemiológicos Guava bacterial blight due to Erwinia psidii: incidence levels and epidemiological aspects

    Directory of Open Access Journals (Sweden)

    Abi Soares Anjos Marques

    2007-01-01

    Full Text Available Um dos fatores limitantes ao cultivo da goiabeira no Brasil é a 'seca dos ponteiros', causada por Erwinia psidii, presente nas regiões Sudeste e Centro-Oeste, onde se concentram grandes áreas produtoras. Considerando a pequena disponibilidade de informações sobre a epidemiologia e níveis de incidência dessa bacteriose, este estudo teve como objetivos: confirmar a distribuição e verificar a dispersão da seca dos ponteiros da goiabeira no Distrito Federal; investigar o efeito da temperatura sobre a multiplicação in vitro de E. psidii; desenvolver um teste de patogenicidade prático e eficiente e avaliar a sobrevivência in vitro da bactéria em diferentes substratos. A doença foi identificada em 56% das propriedades produtoras avaliadas no DF, com 81,9% de correlação entre a presença de sintomas e o diagnóstico laboratorial. A melhor faixa de temperatura para multiplicação de E. psidii foi de 24 a 33 ºC, e a bactéria permaneceu viável por até 120 dias em suspensão em água. A inoculação da bactéria em folhas ou hastes destacadas levou ao aparecimento de sintomas a partir do sétimo dia e mostrou-se eficiente como um teste rápido para se avaliar a patogenicidade de isolados.A major disease that affects guava is 'bacterial blight', caused by Erwinia psidii, which has been reported in Southeastern and Central Regions of Brazil where the major producing areas are located. Considering the lack of information on epidemiology and incidence levels of this disease, the objectives of this study were to confirm the presence and to verify the spread of the disease in Distrito Federal (DF; to determine optimal temperature for in vitro multiplication of E. psidii; to develop a simple and effective method for pathogenicity testing and to evaluate in vitro bacterial survival on different substrates. The disease was detected in 56% of producing orchards evaluated in DF, with a correlation of 81, 9% between presence of symptoms and

  3. Retinol sérico de adolescentes de uma escola da cidade de São Paulo Retinol blood levels in high school students of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Márcia Regina Vítolo

    2004-09-01

    Full Text Available OBJETIVO: Investigar os níveis séricos de retinol de 218 adolescentes de ambos os sexos com idade entre 10 e 19 anos, matriculados em colégio da rede privada de ensino da cidade de São Paulo, foi o objetivo deste trabalho. MÉTODOS: Para a avaliação da condição nutricional dos adolescentes, utilizaram-se as medidas antropométricas de peso e altura e também a história dietética. A dosagem de retinol foi realizada pela técnica de espectrofotometria, considerando como níveis séricos inadequados valores OBJECTIVE: The purpose of the study was to examine plasma retinol levels in 218 adolescents of both sexes, ages 10 to 19 years old. All the subjects attended a private high school in the city of São Paulo. METHODS: In order to evaluate the students' nutritional condition, the researchers performed anthropometrical measurements - weight and height - in addition to investigating the subjects' diet history. The retinol level was measured through the spectrophotometer technique, considering as inadequate values of concentration under <1.05µmol/L (30µg/dL. RESULTS: The results indicate that the average intake, according to the age range, was higher than recommended, even though presenting high deviation patterns for both genders. The percentage of teenagers with plasma concentrations of vitamin A under the adequate level was 30% for both genders, and neither the analysis of the correlation between Body Mass Index and plasma concentrations of retinol, nor the analysis of the correlation between the density of vitamin A intake and plasma concentration of retinol, were significant. CONCLUSION: The research findings point out to the need for further investigation of vitamin A concentrations during adolescence, in order to check more accurately whether the low plasma concentration of this nutrient should be considered a risk factor, or the result of the accelerated absorption which takes place in adolescence to fulfill the metabolic

  4. A Role for D1 Dopamine Receptors in Striatal Methamphetamine-Induced Neurotoxicity

    OpenAIRE

    Friend, Danielle M.; Keefe, Kristen A.

    2013-01-01

    Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 Dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Import...

  5. A role for D1 dopamine receptors in striatal methamphetamine-induced neurotoxicity.

    Science.gov (United States)

    Friend, Danielle M; Keefe, Kristen A

    2013-10-25

    Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. A Plastic Cortico-Striatal Circuit Model of Adaptation in Perceptual Decision

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    Pao-Yueh eHsiao

    2013-12-01

    Full Text Available The ability to optimize decisions and adapt them to changing environments is a crucial brain function that increase survivability. Although much has been learned about the neuronal activity in various brain regions that are associated with decision making, and about how the nervous systems may learn to achieve optimization, the underlying neuronal mechanisms of how the nervous systems optimize decision strategies with preference given to speed or accuracy, and how the systems adapt to changes in the environment, remain unclear. Based on extensive empirical observations, we addressed the question by extending a previously described cortico-basal ganglia circuit model of perceptual decisions with the inclusion of a dynamic dopamine (DA system that modulates spike-timing dependent plasticity. We found that, once an optimal model setting that maximized the reward rate was selected, the same setting automatically optimized decisions across different task environments through dynamic balancing between the facilitating and depressing components of the DA dynamics. Interestingly, other model parameters were also optimal if we considered the reward rate that was weighted by the subject’s preferences for speed or accuracy. Specifically, the circuit model favored speed if we increased the phasic DA response to the reward prediction error, whereas the model favored accuracy if we reduced the tonic DA activity or the phasic DA responses to the estimated reward probability. The proposed model provides insight into the roles of different components of DA responses in decision adaptation and optimization in a changing environment.

  7. Efeitos da laserterapia de baixa potência na reposta oxidativa epidérmica induzida pela cicatrização de feridas Effects of low-level laser therapy on epidermal oxidative response induced by wound healing

    Directory of Open Access Journals (Sweden)

    PCL Silveira

    2009-08-01

    Full Text Available INTRODUÇÃO: O uso terapêutico do laser de baixa potência na fisioterapia tem aumentado significativamente. OBJETIVO: Avaliar os efeitos da laserterapia de baixa potência nos parâmetros oxidativos na cicatrização de feridas em ratos. MÉTODOS: Dezoito ratos Wistar foram divididos randomicamente em 3 grupos (controle 5 dias, n=6; 5 dias/2 J/cm², n=6; 5 dias/4 J/cm², n=6. Uma única ferida circular medindo 8 X 8 mm foi cirurgicamente realizada no dorso do rato. Trinta minutos após a última irradiação, os ratos foram submetidos à eutanásia, e o tecido irradiado foi removido cirurgicamente e armazenado a -70ºC. Foi determinada a atividade das enzimas da cadeia respiratória: DCIP oxirredutase (complexo II e succinato desidrogenase solúvel (SDH, atividade do citocromo c oxidase (complexo IV, produção de ânion superóxido, atividade da superóxido dismutase (SOD e catalase (CAT. A lipoperoxidação foi avaliada pela técnica de TBARS. RESULTADOS: Os resultados mostram uma diminuição na atividade do complexo II nos grupos irradiados por 5 dias com 2 e 4 J/cm², enquanto a produção de ânion superóxido mostrou uma diminuição significativa no grupo irradiado por 5 dias com 4 J/cm² em relação ao grupo controle. Além disso, um aumento significativo na atividade da catalase foi observado no grupo irradiado por 5 dias com 2 J/cm², como também uma diminuição da peroxidação lipídica nos dois grupos irradiados. CONCLUSÕES: Os resultados do presente estudo indicam que o laser estimula a atividade antioxidante e protege a célula contra danos oxidativos durante o processo de cicatrização de feridas cutâneas em ratos.BACKGROUND: Therapeutic use of low-level laser in physical therapy has increased significantly. OBJECTIVE: To assess the effects of low-level laser therapy on the oxidative parameters of wound healing in rats. METHODS: Eighteen Wistar rats were randomly divided into three groups (control, 5 days, n=6; 2 J

  8. Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and volume in humans.

    Science.gov (United States)

    Bertolino, Alessandro; Fazio, Leonardo; Di Giorgio, Annabella; Blasi, Giuseppe; Romano, Raffaella; Taurisano, Paolo; Caforio, Grazia; Sinibaldi, Lorenzo; Ursini, Gianluca; Popolizio, Teresa; Tirotta, Emanuele; Papp, Audrey; Dallapiccola, Bruno; Borrelli, Emiliana; Sadee, Wolfgang

    2009-01-28

    Dopamine modulation of neuronal activity during memory tasks identifies a nonlinear inverted-U shaped function. Both the dopamine transporter (DAT) and dopamine D(2) receptors (encoded by DRD(2)) critically regulate dopamine signaling in the striatum and in prefrontal cortex during memory. Moreover, in vitro studies have demonstrated that DAT and D(2) proteins reciprocally regulate each other presynaptically. Therefore, we have evaluated the genetic interaction between a DRD(2) polymorphism (rs1076560) causing reduced presynaptic D(2) receptor expression and the DAT 3'-VNTR variant (affecting DAT expression) in a large sample of healthy subjects undergoing blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging (MRI) during memory tasks and structural MRI. Results indicated a significant DRD(2)/DAT interaction in prefrontal cortex and striatum BOLD activity during both working memory and encoding of recognition memory. The differential effect on BOLD activity of the DAT variant was mostly manifest in the context of the DRD(2) allele associated with lower presynaptic expression. Similar results were also evident for gray matter volume in caudate. These interactions describe a nonlinear relationship between compound genotypes and brain activity or gray matter volume. Complementary data from striatal protein extracts from wild-type and D(2) knock-out animals (D2R(-/-)) indicate that DAT and D(2) proteins interact in vivo. Together, our results demonstrate that the interaction between genetic variants in DRD(2) and DAT critically modulates the nonlinear relationship between dopamine and neuronal activity during memory processing.

  9. THE LEVELS OF SELENIUM IN CERRADOS PASTURES AND THE EFFECTS OF ITS SUPPLEMENTATION IN PERFORMANCE OF LAMBS NÍVEIS DE SELÊNIO EM PASTAGENS DE CERRADO E EFEITOS DA SUPLEMENTAÇÃO SOBRE O DESEMPENHO DE CORDEIROS

    Directory of Open Access Journals (Sweden)

    José Henrique Stringhini

    2007-09-01

    Full Text Available

    This experiment was carried out in the Água Limpa Farm, of the University of Brasília, aiming to estimate the level of selenium and its variation during the year in some cultivated pastures of the cerrados region (Andropogon gayanus var. bisquamulatus, Brachiaria decumbens and Brachiaria ruziziensis. On the other hand, it was determined the effects of the supplementation, through intramuscular applications, in 24 Bergamacia weaned lambs. Pastures samples were collected trying to simulate the animal grazing, at intervals of 84 days, and different chemical methods of determination of selenium were evaluated. The fluorometric method has the best response and the levels of the samples varied from 0.025 to 0.075 ppm. In relation to the lambs, difference in weight gains were not statistically significant (P>0.05.

    KEY-WORDS: Brazilian savannas (“cerrados”; sheep; selenium supplementation.

    O presente experimento foi conduzido na Fazenda Água Limpa, da Universidade de Brasília, e teve como objetivos verificar os níveis estacionais de selênio encontrados nas pastagens de Andropogon gayanus var. bisquamulatus, Brachiaria decunbens e Brachiaria ruziziensis e avaliar os efeitos da suplementação de selênio por via intramuscular em 24 ovinos desmamados da raça Bergamácia. Foram efetuadas quatro coletas de forragem procurando imitar o pastejo dos animais e testados os métodos químicos para análise de selênio. O método fluorométrico foi o mais adequado e determinaram-se os níveis que variaram entre 0,025 e 0,075 ppm para as pastagens estudadas. Com relação aos cordeiros, não se observou efeito significativo para o ganho de peso dos cordeiros (P>0

  10. Validade da hipertensão autorreferida associa-se inversamente com escolaridade em brasileiros Validity of self-reported hypertension is inversely associated with the level of education in Brazilian individuals

    Directory of Open Access Journals (Sweden)

    Soraya Sant'Ana de Castro Selem

    2012-01-01

    Full Text Available FUNDAMENTO: A hipertensão autorreferida é um dado de interesse para saúde pública e acessível em estudos epidemiológicos, cuja validade deve ser verificada para o adequado emprego dessa informação. OBJETIVO: Verificar a validade da hipertensão autorreferida e os fatores associados em adultos e idosos na cidade de São Paulo, Brasil. MÉTODOS: Foram selecionados participantes do estudo transversal de base populacional Inquérito de Saúde no Município de São Paulo (ISA-Capital 2008 com 20 anos ou mais, de ambos os sexos, que tiveram sua pressão arterial aferida (n = 535. A hipertensão foi definida como Pressão arterial > 140/90 mmHg e/ou uso de medicamentos para hipertensão. Foram calculados sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e coeficiente Kappa. A regressão de Poisson foi utilizada para identificar os fatores associados à sensibilidade da hipertensão autorreferida. RESULTADOS: A sensibilidade da hipertensão autorreferida foi 71,1% (IC95%: 64,8-76,9, especificidade 80,5% (IC95%: 75,6-84,8, valor preditivo positivo 73,7% (IC95%: 67,4-79,3, e valor preditivo negativo 78,5% (IC95%: 73,5-82,9. Houve concordância moderada entre hipertensão autorreferida e diagnóstico de hipertensão pela pressão arterial aferida (kappa = 0,52; IC95%: 0,45-0,59. Índice de massa corporal e escolaridade associaram-se independentemente à sensibilidade (índice de massa corporal > 25 kg/m²: RP = 1,42; IC95%: 1,15-1,76; escolaridade > 9 anos: RP=0,71; IC95%: 0,54-0,94. CONCLUSÃO: A hipertensão autorreferida mostrou-se válida em adultos e idosos no município de São Paulo, sendo um indicador apropriado para vigilância da prevalência da hipertensão, na ausência da pressão arterial medida. Sobrepeso associou-se positivamente à validade da hipertensão autorreferida. Outros estudos são necessários para elucidar a relação inversa entre a validade da hipertensão autorreferida e a escolaridade

  11. Validade da hipertensão autorreferida associa-se inversamente com escolaridade em brasileiros Validity of self-reported hypertension is inversely associated with the level of education in Brazilian individuals

    Directory of Open Access Journals (Sweden)

    Soraya Sant'Ana de Castro Selem

    2013-01-01

    Full Text Available FUNDAMENTO: A hipertensão autorreferida é um dado de interesse para saúde pública e acessível em estudos epidemiológicos, cuja validade deve ser verificada para o adequado emprego dessa informação. OBJETIVO: Verificar a validade da hipertensão autorreferida e os fatores associados em adultos e idosos na cidade de São Paulo, Brasil. MÉTODOS: Foram selecionados participantes do estudo transversal de base populacional Inquérito de Saúde no Município de São Paulo (ISA-Capital 2008 com 20 anos ou mais, de ambos os sexos, que tiveram sua pressão arterial aferida (n = 535. A hipertensão foi definida como Pressão arterial > 140/90 mmHg e/ou uso de medicamentos para hipertensão. Foram calculados sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e coeficiente Kappa. A regressão de Poisson foi utilizada para identificar os fatores associados à sensibilidade da hipertensão autorreferida. RESULTADOS: A sensibilidade da hipertensão autorreferida foi 71,1% (IC95%: 64,8-76,9, especificidade 80,5% (IC95%: 75,6-84,8, valor preditivo positivo 73,7% (IC95%: 67,4-79,3, e valor preditivo negativo 78,5% (IC95%: 73,5-82,9. Houve concordância moderada entre hipertensão autorreferida e diagnóstico de hipertensão pela pressão arterial aferida (kappa = 0,52; IC95%: 0,45-0,59. Índice de massa corporal e escolaridade associaram-se independentemente à sensibilidade (índice de massa corporal > 25 kg/m²: RP = 1,42; IC95%: 1,15-1,76; escolaridade > 9 anos: RP=0,71; IC95%: 0,54-0,94. CONCLUSÃO: A hipertensão autorreferida mostrou-se válida em adultos e idosos no município de São Paulo, sendo um indicador apropriado para vigilância da prevalência da hipertensão, na ausência da pressão arterial medida. Sobrepeso associou-se positivamente à validade da hipertensão autorreferida. Outros estudos são necessários para elucidar a relação inversa entre a validade da hipertensão autorreferida e a escolaridade

  12. Relação materno-filial da raça Morada Nova recebendo dietas com três níveis de energia, ao final da gestação Ewe-lambs relationship in Morada Nova breed under three energy levels at the end of gestation

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    Tobyas Maia de Albuquerque Mariz

    2007-12-01

    Full Text Available Objetivou-se com este trabalho avaliar os efeitos de diferentes níveis de energia ofertados no terço final da gestação sobre o comportamento materno-filial de animais da raça Morada Nova. O experimento consistiu de três tratamentos - três grupos de oito matrizes, alimentadas com dietas isoprotéicas contendo diferentes níveis energéticos (2,0; 2,4 e 2,8 Mcal EM/kg MS, com oito repetições cada. Observou-se efeito dos tratamentos sobre as variáveis comportamentais maternas avaliadas (vocalização, ato de cheirar e lamber a cria e a posição da ovelha em - pé ou deitada, nas ovelhas, mas não foi observada diferença para os comportamentos filiais (posição da cria, tempo decorrido do nascimento à primeira vez que ficou de pé, tempo decorrido do nascimento à primeira mamada, tempo total de mamadas dos cordeiros. A mobilização de reservas ou o carreamento direto de nutrientes da dieta para o crescimento fetal normal, nos grupos alimentos com dietas contendo 2,0 e 2,4 Mcal EM/kg MS, minimizaram os possíveis efeitos sobre o comportamento filial dos cordeiros. Mesmo sob interferência no relacionamento com as crias, ovelhas Morada Nova conseguiram manter as condições dos cordeiros inalteradas em todos os tratamentos.The present work was carried out with the objective to evaluate the effects of different energy levels offered in the final third of gestation on the ewe-lambs behavior of animals from the Morada Nova breed. The experiment was divided into three treatments - three groups of eight ewes, fed isoprotein diets containing different energy levels (2.0, 2.4, and 2.8 Mcal ME/kg DM, with eight replicates each. There was effect of the treatment on the maternal behavior evaluated variables (vocalization, act of smell and lick the lambs and the position of the ewe - stand up or lying, in the ewes, but no difference was observed for the filial behavior (position of animal, time from the birth to the first time that the animal was

  13. The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET.

    Science.gov (United States)

    Caravaggio, Fernando; Ku Chung, Jun; Plitman, Eric; Boileau, Isabelle; Gerretsen, Philip; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel

    2017-11-01

    Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D 2/3 receptors (D 2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D 2/3 R availability measured with an antagonist radiotracer ([ 11 C]-raclopride) versus an agonist radiotracer ([ 11 C]-(+)-PHNO) were examined. Data from 62 subjects scanned with [ 11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [ 11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. For [ 11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BP ND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BP ND in the VS. With [ 11 C]-raclopride, BP ND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BP ND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D 2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function.

    Science.gov (United States)

    Sarter, Martin; Albin, Roger L; Kucinski, Aaron; Lustig, Cindy

    2014-07-01

    Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson's disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive-behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional-motor integration by striatal circuitry. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function

    Science.gov (United States)

    Sarter, Martin; Albin, Roger L.; Kucinski, Aaron; Lustig, Cindy

    2015-01-01

    Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson’s disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive–behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional–motor integration by striatal circuitry. PMID:24805070

  16. Elevação da lipase e amilase no doente crítico: estudo retrospectivo Increased lipase and amilase levels in critically ill patients: retrospective study

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    Margarida Ferreira

    2008-12-01

    Full Text Available OBJETIVOS: A elevação da lipase e amilase séricas são frequentemente encontradas em doentes internados em unidade de terapia intensiva sem que exista doença pancreática prévia, constituindo um desafio diagnóstico e terapêutico. Baseados nesta evidência os autores propuseram-se a determinar a incidência de hiperlipasemia assintomática nos doentes críticos, fatores desencadeantes e evolução clínica destes doentes. MÉTODOS: Estudo retrospectivo dos doentes internados na unidade de terapia intensiva de 1 de janeiro a 31 de dezembro de 2006, excluídas internações por pancreatite aguda, história de patologia pancreática, insuficiência renal ou falta de dados. Pacientes foram distribuídos em dois grupos (com e sem hiperlipasemia e feita comparação considerando diversas variáveis clínicas, laboratoriais, imagiológicas. Análise estatística: SPSS 13; testes t de Student e qui² (IC 95%, com significância estatística se p38 ºC (pOBJECTIVES: Elevated lipase and amylase are commonly found in patients in intensive care unit without a previously recognized pancreatic illness, constituting a diagnostic and therapeutic challenge. The authors therefore proposed to determine the frequency of asymptomatic high serum lipase in critically ill patients, involved risk factors and outcome. METHODS: Retrospective study of patients admitted in an intensive care unit from January 1 to December 31, 2006, excluding admissions for acute pancreatitis, history of pancreatic disease, renal insufficiency or lacking of data. Patients were divided in two groups (with and without high serum lipase that were compared for clinical, laboratory and radiological variables. Statistical analysis: SPSS 13; Student's t test and Chi-square test (CI 95% with statistical significance if p< 0.05. RESULTS: 102 patients were included with high serum lipase was present in 39.2% of patients, mean lipase of 797U/L. Patients with high serum lipase had longer hospital

  17. Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

    Science.gov (United States)

    Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

    2016-01-01

    Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID

  18. Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites

    Science.gov (United States)

    Oliveira, Rodrigo F.; Kim, MyungSook; Blackwell, Kim T.

    2012-01-01

    Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity. PMID:22346744

  19. Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology.

    Science.gov (United States)

    Payer, Doris E; Park, Min Tae M; Kish, Stephen J; Kolla, Nathan J; Lerch, Jason P; Boileau, Isabelle; Chakravarty, M M

    2015-01-01

    Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects. Subjects reporting PD-Sx were then grouped into symptom-based clusters: N = 20 into Cluster B (reporting Antisocial, Borderline, Histrionic, or Narcissistic PD-Sx) and N = 28 into Cluster C (reporting Obsessive-Compulsive, Avoidant, or Dependent PD-Sx); N = 11 subjects reported PD-Sx from both clusters, and none reported Cluster A (Paranoid, Schizoid, or Schizotypal) PD-Sx. Compared to control, Cluster C PD-Sx was associated with greater striatal surface area localized to the caudate tail, smaller ventral striatum volumes, and greater cortical thickness in right prefrontal cortex. Both Cluster B and C PD-Sx groups also showed trends toward greater posterior caudate volumes and orbitofrontal surface area anomalies, but these findings did not survive correction for multiple comparisons. The results point to morphological abnormalities that could contribute to Cluster C PD-Sx. In addition, the observations parallel those in substance use disorders, pointing to the importance of considering PD-Sx when interpreting findings in often-comorbid psychiatric disorders.

  20. Distinct roles of synaptic and extrasynaptic GABAA receptors in striatal inhibition dynamics

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    Ruixi eLuo

    2013-11-01

    Full Text Available Striatonigral and striatopallidal projecting medium spiny neurons (MSNs express dopamine D1 (D1+ and D2 receptors (D2+, respectively. Both classes receive extensive GABAergic input via expression of synaptic, perisynaptic and extrasynaptic GABAA receptors. The activation patterns of different presynaptic GABAergic neurons produce transient and sustained GABAA receptor-mediated conductance that fulfill distinct physiological roles. We performed single and dual whole cell recordings from striatal neurons in mice expressing fluorescent proteins in interneurons and MSNs. We report specific inhibitory dynamics produced by distinct activation patterns of presynaptic GABAergic neurons as source of synaptic, perisynaptic and extrasynaptic inhibition. Synaptic GABAA receptors in MSNs contain the α2, γ2 and a β subunit. In addition, there is evidence for the developmental increase of the α1 subunit that contributes to faster inhibitory postsynaptic current (IPSC. Tonic GABAergic currents in MSNs from adult mice are carried by extrasynaptic receptors containing the α4 and δ subunit, while in younger mice this current is mediated by receptors that contain the α5 subunit. Both forms of tonic currents are differentially expressed in D1+ and D2+ MSNs. This study extends these findings by relating presynaptic activation with pharmacological analysis of inhibitory conductance in mice where the β3 subunit is conditionally removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the δ subunit. Our results show that responses to low doses of gaboxadol (2μM, a GABAA receptor agonist with preference to δ subunit, are abolished in the δ but not the β3 subunit knock out mice. This suggests that the β3 subunit is not a component of the adult extrasynaptic receptor pool, in contrast to what has been shown for tonic current in young mice. Deletion of the β3 subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its

  1. Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

    Science.gov (United States)

    Schreiter, S; Spengler, S; Willert, A; Mohnke, S; Herold, D; Erk, S; Romanczuk-Seiferth, N; Quinlivan, E; Hindi-Attar, C; Banzhaf, C; Wackerhagen, C; Romund, L; Garbusow, M; Stamm, T; Heinz, A; Walter, H; Bermpohl, F

    2016-11-01

    Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

  2. Input dependent cell assembly dynamics in a model of the striatal medium spiny neuron network

    Directory of Open Access Journals (Sweden)

    Adam ePonzi

    2012-03-01

    Full Text Available The striatal medium spiny neuron (MSNs network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri stimulus time histograms (PSTH of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioural task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviourally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would in when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and delineate the range of parameters where this behaviour is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response

  3. Input dependent cell assembly dynamics in a model of the striatal medium spiny neuron network.

    Science.gov (United States)

    Ponzi, Adam; Wickens, Jeff

    2012-01-01

    The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioral task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviorally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and outline the range of parameters where this behavior is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response which could be utilized by the animal in behavior.

  4. Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.

    Science.gov (United States)

    Mickey, Brian J; Sanford, Benjamin J; Love, Tiffany M; Shen, Pei-Hong; Hodgkinson, Colin A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-07-04

    Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable