WorldWideScience

Sample records for neuroleptic-treated rat striatum

  1. Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

    International Nuclear Information System (INIS)

    Emson, P.C.; Westmore, K.; Augood, S.J.

    1996-01-01

    The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [ 35 S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [ 35 S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase-positive cells

  2. Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

    Energy Technology Data Exchange (ETDEWEB)

    Emson, P C; Westmore, K; Augood, S J [MRC Molecular Neuroscience Group, The Department of Neurobiology, The Babraham Institute, Babraham, Cambridge (United Kingdom)

    1996-12-11

    The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [{sup 35}S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [{sup 35}S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase

  3. Gene expression in rat striatum following carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Shuichi Hara

    2017-06-01

    Full Text Available Carbon monoxide (CO poisoning causes brain damage, which is attenuated by treatment with hydrogen [1,2], a scavenger selective to hydroxyl radical (·≡OH [3]. This suggests a role of ·≡OH in brain damage due to CO poisoning. Studies have shown strong enhancement of ·≡OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb level >70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with ·≡OH production [5] might contribute to ·≡OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO database under accession number GSE94780.

  4. Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

    Science.gov (United States)

    Baker, Phillip M.; Ragozzino, Michael E.

    2014-01-01

    Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

  5. [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

    Science.gov (United States)

    Liu, Ping; He, Xinrong; Guo, Mei

    2010-04-01

    To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

  6. Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

    Directory of Open Access Journals (Sweden)

    Pamphyle Abedi Mukutenga

    2012-08-01

    Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

  7. Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats.

    Science.gov (United States)

    Haleagrahara, Nagaraja; Siew, Cheng Jun; Ponnusamy, Kumar

    2013-02-01

    The catecholaminergic neurotoxin 6-hydroxydopamine is used to lesion dopaminergic pathways in the experimental animal models of Parkinson's disease. The present study was aimed to evaluate the combined treatment with bioflavonoid quercetin (QN) and desferrioxamine (DFO) on 6-hydroxydopamine (6-OHDA) - induced neurotoxicity in the striatum of rats. Adult, male Sprague - Dawley rats were divided into control, sham lesion, 6-OHDA treated (300 µg, intracisternal), 6-OHDA with QN (50 mg/kg) treated, 6-OHDA with DFO (50 mg/kg) treated and 6-OHDA with QN and DFO treated groups. Striatal dopamine, protein carbonyl content (PCC), glutathione (GSH) and superoxide dismutase (SOD) were estimated. There was a significant increase (p protection. Combined treatment has a more significant effect (p protecting the neurons and increasing the antioxidant enzymes in the striatum. In conclusion, an antioxidant with iron chelator treatment showed a significant neuroprotective effect against 6-hydroxydopamine (6-OHDA) by preventing dopaminergic neuronal loss and maintaining the striatal dopamine level.

  8. Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

    Directory of Open Access Journals (Sweden)

    Haiyan Jiang

    2018-05-01

    Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

  9. Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.

    Directory of Open Access Journals (Sweden)

    Ippolita Cantuti-Castelvetri

    2010-11-01

    Full Text Available Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.Quantitative real-time polymerase chain reaction (PCR was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.

  10. Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Shim, In Sop [Kyunghee University, Seoul (Korea, Republic of); Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2002-10-01

    We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants.

  11. Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Shim, In Sop; Chung, June Key; Lee, Myung Chul

    2002-01-01

    We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants

  12. Haloperidol-induced changes in neuronal activity in the striatum of the freely moving rat

    Directory of Open Access Journals (Sweden)

    Dorin eYael

    2013-12-01

    Full Text Available The striatum is the main input structure of the basal ganglia, integrating input from the cerebral cortex and the thalamus, which is modulated by midbrain dopaminergic input. Dopamine modulators, including agonists and antagonists, are widely used to relieve motor and psychiatric symptoms in a variety of pathological conditions. Haloperidol, a dopamine D2 antagonist, is commonly used in multiple psychiatric conditions and motor abnormalities. This article reports the effects of haloperidol on the activity of three major striatal subpopulations: medium spiny projection neurons (MSNs, fast spiking interneurons (FSIs and tonically active neurons (TANs. We implanted multi-wire electrode arrays in the rat dorsal striatum and recorded the activity of multiple single units in freely moving animals before and after systemic haloperidol injection. Haloperidol decreased the firing rate of FSIs and MSNs while increasing their tendency to fire in an oscillatory manner in the high voltage spindle (HVS frequency range of 7-9 Hz. Haloperidol led to an increased firing rate of TANs but did not affect their non-oscillatory firing pattern and their typical correlated firing activity. Our results suggest that dopamine plays a key role in tuning both single unit activity and the interactions within and between different subpopulations in the striatum in a differential manner. These findings highlight the heterogeneous striatal effects of tonic dopamine regulation via D2 receptors which potentially enable the treatment of diverse pathological states associated with basal ganglia dysfunction.

  13. Release of /sup 3/H-. cap alpha. -methyl-m-tyramine from rat striatum in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dorris, R L [Baylor College of Dentistry, Dallas, Tex. (USA). Dept. of Pharmacology

    1976-01-01

    Release of /sup 3/H-d-..cap alpha..-methyl-m-tyramine (/sup 3/H-MMTA), a false dopaminergic transmitter from rat striatum was studied in vitro. After its initial uptake, /sup 3/H-MMTA was released by high K/sup +/ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that /sup 3/H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.

  14. Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

    International Nuclear Information System (INIS)

    Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita; Pope, Carey

    2006-01-01

    This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted in any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some

  15. Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

    Directory of Open Access Journals (Sweden)

    Julie eBoulanger Bertolus

    2014-05-01

    Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

  16. Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

    Science.gov (United States)

    Gomez, Gimena; Saborido, Mariano D; Bernardi, M Alejandra; Gershanik, Oscar S; Taravini, Irene R; Ferrario, Juan E

    2018-02-14

    L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

    International Nuclear Information System (INIS)

    Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

    2013-01-01

    In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

  18. Change of striatum dopaminergic transporter and content of dopamine in rats with experimental hyperthyroidism

    International Nuclear Information System (INIS)

    Lin Yansong; Wang Huicheng; Zhao Zhiying; Zhu Li; Zhang Yingqiang; Chen Zhengping

    2009-01-01

    Objective: The central dopamine system plays an important role in regulating movement and mood. In our routine clinical practice,we found that patients with hyperthyroidism often show tremor of their hands or legs. Meanwhile they also experienced emotional problems such as anxiety and depression. These reminded us that there might be close relationship between thyroid hormone and dopamine system. Based on our previous works, in this study we evaluated the change of striatum dopamine transporter (DAT) by using 99 Tc m -2β- [N, N'-bis (2-merecaptoethyl) ethylenediamino]methyl, 3β- (4-chlorophenyl) tropane (TRODAT-1) brain biodistribution, and the content of striatum dopamine and its metabolites 3.4-di-hydroxyphenylacetic (DOPAC) by high performace liquid chromatograph-electrochemical detection (HPLC-ECD) in rats with experimental hyperthyroidism. Methods: All 24 rats were randomly divided into two groups, thyroxin group were induced by daily thyroxin infusion for 14 d to be experimental hyperthyroidism, the others were control group which received saline infusion. The blood samples were randomly taken from thyroxine group and control group, and the concentration of TT 3 and TT 4 were detected by radioimmunoassay. After 14 d,both experimental (thyroxine group) and control group were further divided into 2 sub-groups. One was for evaluation of the function of striatum DAT by 99 Tc m -TRODAT-1 biodistribution study and the other was for HPIJC-ECD measurement of the concentration of dopamine and its metabolites DOPAC. Results: Significantly hyperactivity and weight loss [(223.90 ± 8.40) VS (261.60 ± 14.20)g, t=6.98. P 3 and TT 4 after thyroxin infusion was significantly elevated than that of before thyroxin infusion [(2.72 ± 0.29) V8(1.46 ± 0.17) nmol/L, t=10.51, P 3 , and TT 4 after saline infusion showed no statistical significance as compared with before saline infusion [(1.71 ± 0.20) vs (1.54 ± O.09) nmol/L, t=1.68. P>0.05 and (88.38 ± 6.76) vs (98.38 ± 9

  19. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  20. Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Mathew Jobin

    2009-04-01

    Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

  1. Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo

    NARCIS (Netherlands)

    W.N. Sloot (W.); J. Korf (Jakob); J.F. Koster (Johan); L.E.A. de Wit (Elly); J.-B.P. Gramsbergen (J. B P)

    1996-01-01

    textabstractThe present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals (.OH) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA)

  2. Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum.

    Science.gov (United States)

    de Oliveira, Iris Machado; Nunes, Brenda Viviane Ferreira; Barbosa, Durán Rafael; Pallares, Alfonso Miguel; Faro, Lilian Rosana Ferreira

    2010-02-15

    Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC. Intrastriatal administration of 1mM or 5mM TMX has not produced significant increases on dopamine (DA) levels, nonetheless the infusion of 10mM TMX increases the DA output to 841+/-132%, when compared to basal levels. Infusion of 1mM CLO has not induced a significant increase in DA levels, even so 2, 3.5 and 5mM CLO have produced an increase of 438+/-8%, 2778+/-598% and 4604+/-516%, respectively, every compared to basal levels. Mecamylamine (MEC), a non-competitive nAChRs antagonist, was used to investigate the role of nAChRs on DA release induced by TMX and CLO. The increases in extracellular DA levels induced by TMX and CLO when associated to MEC are 80% and 68% lower than the effect produced by CLO and TMX isolated. These results confirm that TMX and CLO appear to induce in vivo DA increased release in striatum of rats and it seems to be concentration dependent. Moreover, these results indicate that this effect might be related to nAChRs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  3. Electrical high frequency stimulation in the dorsal striatum: Effects on response learning and on GABA levels in rats.

    Science.gov (United States)

    Schumacher, Anett; de Vasconcelos, Anne Pereira; Lecourtier, Lucas; Moser, Andreas; Cassel, Jean-Christophe

    2011-09-23

    Electrical high frequency stimulation (HFS) has been used to treat various neurological and psychiatric diseases. The striatal area contributes to response learning and procedural memory. Therefore, we investigated the effect of striatal HFS application on procedural/declarative-like memory in rats. All rats were trained in a flooded Double-H maze for three days (4 trials/day) to swim to an escape platform hidden at a constant location. The starting place was the same for all trials. After each training session, HFS of the left dorsal striatum was performed over 4h in alternating 20 min periods (during rest time, 10a.m. to 3p.m.). Nineteen hours after the last HFS and right after a probe trial assessing the rats' strategy (procedural vs. declarative-like memory-based choice), animals were sacrificed and the dorsal striatum was quickly removed. Neurotransmitter levels were measured by HPLC. Stimulated rats did not differ from sham-operated and control rats in acquisition performance, but exhibited altered behavior during the probe trial (procedural memory responses being less frequent than in controls). In stimulated rats, GABA levels were significantly increased in the dorsal striatum on both sides. We suggest that HFS of the dorsal striatum does not alter learning behavior in rats but influences the strategy by which the rats solve the task. Given that the HFS-induced increase of GABA levels was found 19 h after stimulation, it can be assumed that HFS has consequences lasting for several hours and which are functionally significant at a behavioral level, at least under our stimulation (frequency, timing, location, side and strength of stimulation) and testing conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

    Science.gov (United States)

    Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

    2017-10-06

    To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

  5. Glucose Injections into the Dorsal Hippocampus or Dorsolateral Striatum of Rats Prior to T-Maze Training: Modulation of Learning Rates and Strategy Selection

    Science.gov (United States)

    Canal, Clinton E.; Stutz, Sonja J.; Gold, Paul E.

    2005-01-01

    The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial…

  6. The role of dopamine in the nucleus accumbens and striatum during sexual behavior in the female rat.

    Science.gov (United States)

    Becker, J B; Rudick, C N; Jenkins, W J

    2001-05-01

    Dopamine in dialysate from the nucleus accumbens (NAcc) increases during sexual and feeding behavior and after administration of drugs of abuse, even those that do not directly activate dopaminergic systems (e.g., morphine or nicotine). These findings and others have led to hypotheses that propose that dopamine is rewarding, predicts that reinforcement will occur, or attributes incentive salience. Examining increases in dopamine in NAcc or striatum during sexual behavior in female rats provides a unique situation to study these relations. This is because, for the female rat, sexual behavior is associated with an increase in NAcc dopamine and conditioned place preference only under certain testing conditions. This experiment was conducted to determine what factors are important for the increase in dopamine in dialysate from NAcc and striatum during sexual behavior in female rats. The factors considered were the number of contacts by the male, the timing of contacts by the male, or the ability of the female to control contacts by the male. The results indicate that increased NAcc dopamine is dependent on the timing of copulatory stimuli, independent of whether the female rat is actively engaged in regulating this timing. For the striatum, the timing of copulatory behavior influences the magnitude of the increase in dopamine in dialysate, but other factors are also involved. We conclude that increased extracellular dopamine in the NAcc and striatum conveys qualitative or interpretive information about the rewarding value of stimuli. Sexual behavior in the female rat is proposed as a model to determine the role of dopamine in motivated behavior.

  7. Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits

    OpenAIRE

    Mowery, Todd M.; Harrold, Jon B.; Alloway, Kevin D.

    2011-01-01

    The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neur...

  8. Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

    Science.gov (United States)

    Bergstrom, B P; Garris, P A

    1999-03-01

    The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

  9. Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

    Science.gov (United States)

    Holubiec, Mariana I; Romero, Juan I; Blanco, Eduardo; Tornatore, Tamara Logica; Suarez, Juan; Rodríguez de Fonseca, Fernando; Galeano, Pablo; Capani, Francisco

    2017-07-13

    Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

    Science.gov (United States)

    Tobón-Velasco, J C; Palafox-Sánchez, Victoria; Mendieta, Liliana; García, E; Santamaría, A; Chamorro-Cevallos, G; Limón, I Daniel

    2013-08-01

    There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 μg/2 μL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.

  11. Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats.

    Science.gov (United States)

    Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan; Lee, Inah

    2014-11-19

    The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. Copyright © 2014 the authors 0270-6474/14/3415534-14$15.00/0.

  12. Altered dopaminergic regulation of the dorsal striatum is able to induce tic-like movements in juvenile rats

    Science.gov (United States)

    Rizzo, Francesca; Boeckers, Tobias; Schulze, Ulrike

    2018-01-01

    Motor tics are sudden, repetitive, involuntary movements representing the hallmark behaviors of the neurodevelopmental disease Tourette’s syndrome (TS). The primary cause of TS remains unclear. The initial observation that dopaminergic antagonists alleviate tics led to the development of a dopaminergic theory of TS etiology which is supported by post mortem and in vivo studies indicating that non-physiological activation of the striatum could generate tics. The striatum controls movement execution through the balanced activity of dopamine receptor D1 and D2-expressing medium spiny neurons of the direct and indirect pathway, respectively. Different neurotransmitters can activate or repress striatal activity and among them, dopamine plays a major role. In this study we introduced a chronic dopaminergic alteration in juvenile rats, in order to modify the delicate balance between direct and indirect pathway. This manipulation was done in the dorsal striatum, that had been associated with tic-like movements generation in animal models. The results were movements resembling tics, which were categorized and scored according to a newly developed rating scale and were reduced by clonidine and riluzole treatment. Finally, post mortem analyses revealed altered RNA expression of dopaminergic receptors D1 and D2, suggesting an imbalanced dopaminergic regulation of medium spiny neuron activity as being causally related to the observed phenotype. PMID:29698507

  13. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    Science.gov (United States)

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

  14. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  15. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  16. Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum.

    Directory of Open Access Journals (Sweden)

    Peter J Clark

    Full Text Available Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress. Impaired escape behavior is a result of stress-sensitized serotonin (5-HT neuron activity in the dorsal raphe (DRN and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS and lateral (DLS dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.

  17. L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.

    Science.gov (United States)

    Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E

    2017-09-01

    We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.

  18. A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand

    International Nuclear Information System (INIS)

    Ishikawa, Nobuyoshi; Nakamura, Toshihiko; Satou, Motohiro; Takeda, Tohoru; Wu, Jin; Motoji, Naomi; Shigematsu, Akiyo.

    1995-01-01

    Iodo-125-labeled iodobenzamide ([ 125 I]IBZM) is used as a specific binding radioligand to dopamine D 2 receptors with high affinity and selectivity. The radioligand was homogeneously distributed in the whole brain initially after anministration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D 2 receptors in the living brain. (author)

  19. Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum.

    Science.gov (United States)

    Liu, Jing; Parsons, Loren; Pope, Carey

    2015-09-01

    Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

    Science.gov (United States)

    Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

    2009-01-01

    Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

  1. Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

    Science.gov (United States)

    Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

    2009-02-11

    Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

  2. Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Han, Jin; Wan, Hai-Tong; Yang, Jie-Hong; Zhang, Yu-Yan; Ge, Li-Jun; Bie, Xiao-Dong

    2014-01-01

    This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.

  3. Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

    International Nuclear Information System (INIS)

    Hennies, H.H.; Hess, V.; Flohe, L.

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

  4. Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Hennies, H H; Hess, V; Flohe, L

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

  5. Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum.

    Science.gov (United States)

    Melani, Alessia; Corti, Francesca; Stephan, Holger; Müller, Christa E; Donati, Chiara; Bruni, Paola; Vannucchi, Maria Giuliana; Pedata, Felicita

    2012-01-01

    In the central nervous system (CNS) ATP and adenosine act as transmitters and neuromodulators on their own receptors but it is still unknown which part of extracellular adenosine derives per se from cells and which part is formed from the hydrolysis of released ATP. In this study extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under in vivo physiological conditions and after focal ischemia induced by medial cerebral artery occlusion. Under physiological conditions, adenosine and ATP concentrations were in the range of 130 nmol/L and 40 nmol/L, respectively. In the presence of the novel ecto-ATPase inhibitor, PV4 (100 nmol/L), the extracellular concentration of ATP increased 12-fold to ~360 nmol/L but the adenosine concentration was not altered. This demonstrates that, under physiological conditions, adenosine is not a product of extracellular ATP. In the first 4h after ischemia, adenosine increased to ~690 nmol/L and ATP to ~50 nmol/L. In the presence of PV4 the extracellular concentration of ATP was in the range of 450 nmol/L and a significant decrease in extracellular adenosine (to ~270 nmol/L) was measured. The contribution of extracellular ATP to extracellular adenosine was maximal in the first 20 min after ischemia onset. Furthermore we demonstrated, by immunoelectron microscopy, the presence of the concentrative nucleoside transporter CNT2 on plasma and vesicle membranes isolated from the rat striatum. These results are in favor that adenosine is transported in vesicles and is released in an excitation-secretion manner under in vivo physiological conditions. Early after ischemia, extracellular ATP is hydrolyzed by ecto-nucleotidases which significantly contribute to the increase in extracellular adenosine. To establish the contribution of extracellular ATP to adenosine might constitute the basis for devising a correct putative purinergic strategy aimed at protection from ischemic damage

  6. Exploration of D2 receptors and content of DA of striatum in hemi-parkinsonism model rats before and after madopar treatment

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    1998-01-01

    125 I-IBZM autoradiographic analysis, HPLC-ECD were used to study the relationship between D 2 receptors and the content of DA, HVA, DOPAC in striatum of hemi-parkinsonism model rats before and after Madopar treatment. After Madopar treatment, the striatum/cerebellum 125 I-IBZM uptake ratio of lesioned side was 7.23 +- 0.67, showed 17.22 +- 3.94% increasing as compared to the contralateral side, the increasing were significantly declined compared with the pretreatment group and control group (P 2 receptors

  7. Postnatal Administration of Allopregnanolone Modifies Glutamate Release but Not BDNF Content in Striatum Samples of Rats Prenatally Exposed to Ethanol

    Directory of Open Access Journals (Sweden)

    Roberto Yunes

    2015-01-01

    Full Text Available Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c. administered to juvenile male rats (day 21 of age on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8. Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

  8. Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model

    Science.gov (United States)

    Zheng, Deyu; Jiang, Xiaohua; Zhao, Junpeng; Duan, Deyi; Zhao, Huanying; Xu, Qunyuan

    2013-01-01

    The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. PMID:23738148

  9. Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

    Directory of Open Access Journals (Sweden)

    Yin Shou

    2013-01-01

    Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

  10. Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum.

    Science.gov (United States)

    Jupp, Bianca; Murray, Jennifer E; Jordan, Emily R; Xia, Jing; Fluharty, Meg; Shrestha, Saurav; Robbins, Trevor W; Dalley, Jeffrey W

    2016-02-01

    Studies in human and non-human primates demonstrate that social status is an important determinant of cocaine reinforcement. However, it is unclear whether social rank is associated with other traits that also predispose to addiction and whether social status similarly predicts cocaine self-administration in rats. The objective of this study is to investigate whether social ranking assessed using a resource competition task affects (i) the acquisition, maintenance and reinstatement of cocaine self-administration; (ii) the dopaminergic markers in the striatum; and (iii) the expression of ancillary traits for addiction. Social ranking was determined in group-housed rats based upon drinking times during competition for a highly palatable liquid. Rats were then evaluated for cocaine self-administration and cue-induced drug reinstatement or individual levels of impulsivity, anxiety and novelty-induced locomotor activity. Finally, dopamine content, dopamine transporter (DAT) and dopamine D2/D3 (D2/3) receptor binding were measured postmortem in the dorsal and ventral striatum. Rats deemed socially dominant showed enhanced novelty reactivity but were neither more impulsive nor anxious compared with subordinate rats. Dominant rats additionally maintained higher rates of cocaine self-administration but showed no differences in the acquisition, extinction and reinstatement of this behaviour. D2/3 binding was elevated in the nucleus accumbens shell and dorsal striatum of dominant rats when compared to subordinate rats, and was accompanied by elevated DAT and reduced dopamine content in the nucleus accumbens shell. These findings show that social hierarchy influences the rate of self-administered cocaine but not anxiety or impulsivity in rats. Similar to non-human primates, these effects may be mediated by striatal dopaminergic systems.

  11. Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

    Science.gov (United States)

    Parveen, Arshiya; Rizvi, Syed Husain Mustafa; Mahdi, Farzana; Tripathi, Sandeep; Ahmad, Iqbal; Shukla, Rajendra K.; Khanna, Vinay K.; Singh, Ranjana; Patel, Devendra K.; Mahdi, Abbas Ali

    2014-11-01

    Extensive uses of silica nanoparticles (SiNPs) in biomedical and industrial fields have increased the risk of exposure, resulting concerns about their safety. We focussed on some of the safety aspects by studying neurobehavioural impairment, oxidative stress (OS), neurochemical and ultrastructural changes in corpus striatum (CS) of male Wistar rats exposed to 80-nm SiNPs. Moreover, its role in inducing mitochondrial and endoplasmic reticulum (ER) stress-mediated neuronal apoptosis was also investigated. The results demonstrated impairment in neurobehavioural indices, and a significant increase in lipid peroxide levels (LPO), hydrogen peroxide (H2O2), superoxide (O2 -) and protein carbonyl content, whereas there was a significant decrease in the activities of the enzymes, manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), catalase (CAT) and reduced glutathione (GSH) content, suggesting impaired antioxidant defence system. Protein (cytochrome c, Bcl-2, Bax, p53, caspase-3, caspase 12 and CHOP/Gadd153) and mRNA (Bcl-2, Bax, p53 and CHOP/Gadd153, cytochrome c) expression studies of mitochondrial and ER stress-related apoptotic factors suggested that both the cell organelles were involved in OS-mediated apoptosis in treated rat brain CS. Moreover, electron microscopic studies clearly showed mitochondrial and ER dysfunction. In conclusion, the result of the study suggested that subchronic SiNPs' exposure has the potential to alter the behavioural activity and also to bring about changes in biochemical, neurochemical and ultrastructural profiles in CS region of rat brain. Furthermore, we also report SiNPs-induced apoptosis in CS, through mitochondrial and ER stress-mediated signalling.

  12. In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning

    International Nuclear Information System (INIS)

    Gallagher, M.; Bizon, J.L.; Nicolle, M.M.

    1996-01-01

    Using in vitro autoradiography, we investigated [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [ 3 H]kainate and [ 3 H]N-methyl-d-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [ 3 H]kainate binding in CA3 were reduced. In contrast, N-methyl-d-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [ 3 H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-d-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [ 3 H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-d-aspartate binding in the striatum and [ 3 H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability.Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not neccessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial learning, suggesting a compensatory reduction

  13. Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-11-03

    The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

  14. Identification of the D-1 dopamine receptor subunit in rat striatum after photoaffinity labeling

    Energy Technology Data Exchange (ETDEWEB)

    Kuno, T; Tanaka, C [Kobe Univ. (Japan). School of Medicine

    1982-12-28

    When rat striatal membranes, photolabeled with (/sup 3/H)dopamine under assay conditions similar to those used for dopamine-sensitive adenylate cyclase, were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, several radioactively labeled bands appeared. Labeling of these bands was reduced in the presence of non-radioactive dopamine during photolysis, but was unaffected by the presence of sulpiride. Haloperidol preferentially reduced the labeling of the main band which had a molecular weight of about 57,000 rather than the other weakly labeled bands. Labeling of this 57,000 dalton protein was not apparent when rat cerebellar membranes were used and was markedly eliminated by kainic acid-induced lesions that destroyed the intrastriatal nerve cell bodies. These results indicate that this 57,000 dalton protein is the binding subunit of the D-1 dopamine receptor.

  15. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F.; Govoni, S.; Rius, R.A.; Spano, P.F.; Trabucchi, M.

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  16. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F; Govoni, S; Rius, R A; Spano, P F; Trabucchi, M

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  17. Cerebral Oxygenation of the Cortex and Striatum following Normobaric Hyperoxia and Mild Hypoxia in Rats by EPR Oximetry using Multi-Probe Implantable Resonators

    Science.gov (United States)

    Hou, Huagang; Li, Hongbin; Dong, Ruhong; Mupparaju, Sriram; Khan, Nadeem; Swartz, Harold

    2013-01-01

    Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO2) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO2 was measured simultaneously in the cerebral cortex and striatum in the same rats before, during, and after normobaric hyperoxia and mild hypoxia challenges. The baseline mean tissue pO2 values (±SE) were not significantly different between the cortex and striatum. During 30 min of 100% O2 inhalation, a statistically significant increase in tissue pO2 of all four sites was observed, however, the tissue pO2 of the striatum area was significantly higher than in the forelimb area of the cortex. Brain pO2 significantly decreased from the baseline value during 15 min of 15% O2 challenge. No differences in the recovery of the cerebral cortex and striatum pO2 were observed when the rats were allowed to breathe 30% O2. It appears that EPR oximetry using implantable resonators can provide information on pO2 under the experimental conditions needed for such a study. The levels of pO2 that occurred in these experiments are readily resolvable by multi-site EPR oximetry with multi-probe resonators. In addition, the ability to simultaneously measure the pO2 in several areas of the brain provides important information that could potentially help differentiate the pO2 changes that can occur due to global or local mechanisms. PMID:21445770

  18. Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat.

    Science.gov (United States)

    Zhou, Ligang; Furuta, Takahiro; Kaneko, Takeshi

    2004-12-06

    Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. 2004 Wiley-Liss, Inc.

  19. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...

  20. Role of presynaptic receptors in the release and synthesis of /sup 3/H-dopamine by slices of rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, T C; Besson, M J; Giorguieff, M F; Glowinski, J [Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France). Groupe de Neuropharmacologie Biochimique

    1976-01-01

    Striatal slices were continuously superfused with L-3,5-/sup 3/H-Tyrosine(50..mu..Ci/ml) and /sup 3/H-H/sub 2/O (index of /sup 3/H-dopamine (/sup 3/H-DA) synthesis) and /sup 3/H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k/sup +/ for 7.5 min induced a marked increase in /sup 3/H-DA release and a biphasic effect on synthesis. The decrease in the rate of /sup 3/H-H/sub 2/O formation induced by K/sup +/ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked /sup 3/H-DA uptake (10/sup -6/M) it potentiated /sup 3/H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10/sup -6/M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10/sup -6/M) significantly prevented the decrease in /sup 3/H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.

  1. The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum

    International Nuclear Information System (INIS)

    Westfall, T.C.; Besson, M.J.; Giorguieff, M.F.; Glowinski, J.

    1976-01-01

    Striatal slices were continuously superfused with L-3,5- 3 H-Tyrosine(50μCi/ml) and 3 H-H 2 O [index of 3 H-dopamine ( 3 H-DA) synthesis] and 3 H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k + for 7.5 min induced a marked increase in 3 H-DA release and a biphasic effect on synthesis. The decrease in the rate of 3 H-H 2 O formation induced by K + was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3 H-DA uptake (10 -6 M) it potentiated 3 H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10 -6 M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10 -6 M) significantly prevented the decrease in 3 H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter. (orig.) [de

  2. Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo.

    Science.gov (United States)

    Mao, Li-Min; Wang, John Q

    2015-12-01

    Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits.

    Science.gov (United States)

    Mowery, Todd M; Harrold, Jon B; Alloway, Kevin D

    2011-05-01

    The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neurons in the DLS responded to both directions of movement. The latency and magnitude of these neuronal responses displayed very little variation with changes in the rate (2, 5, or 8 Hz) of whisker stimulation. Simultaneous recordings in SI barrel cortex and the DLS revealed important distinctions in the neuronal responses of these serially connected brain regions. In contrast to DLS neurons, SI neurons were activated by the initial deflection of the whiskers but did not respond when the whiskers moved back to their original position. As the rate of whisker stimulation increased, SI responsiveness declined, and the latencies of the responses increased. In fact, when whiskers were deflected at 5 or 8 Hz, many neurons in the DLS responded before the SI neurons. These results and earlier anatomic findings suggest that a component of the sensory-induced response in the DLS is mediated by inputs from the thalamus. Furthermore, the lack of sensory adaptation in the DLS may represent a critical part of the neural mechanism by which the DLS encodes stimulus-response associations that trigger motor habits and other stimulus-evoked behaviors that are not contingent on rewarded outcomes.

  4. Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

    Science.gov (United States)

    Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

    2014-03-01

    We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

    Directory of Open Access Journals (Sweden)

    Matthijs A A Van Der Meer

    2009-06-01

    Full Text Available Local field potential (LFP oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson’s disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45-55 Hz and gamma-80 (70-85 Hz oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

  6. Correlation between (3H)dopamine specific uptake and (3H)GBR 12783 specific binding during the maturation of rat striatum

    International Nuclear Information System (INIS)

    Bonnet, J.J.; Costentin, J.

    1989-01-01

    The development of the specific uptake of dopamine in the rat striatum during the early postnatal period is compared with the ontogenetic changes of the specific binding of ( 3 H)GBR 12783 to the site of uptake inhibition. During maturation, the increase in the specific binding of ( 3 H)GBR 12783 parallels the increase in the specific uptake of dopamine. ( 3 H)GBR 12783 specific binding sites increase in number from day 1 postpartum until 40 days, when they reach the adult level. In 40 day-old rats, the weight of the striatum represents 80% of adult values. The affinity of ( 3 H)GBR 12783 for the inhibition site is similar in membrane preparations obtained from 6 day-old pups and adults; this results in a same ability of the inhibitor to block the specific uptake of dopamine into synaptosomes obtained from pups or adult rats. These data support the hypothesis of the existence of a single molecular entity including both the inhibition site and the carrier itself

  7. Expression of c-fos and c-jun proteins in the marginal division of the rat striatum during learning and memory training

    Institute of Scientific and Technical Information of China (English)

    BAO Xin-min; SHU Si-yun; WANG Hong

    2005-01-01

    Background A new brain region, the marginal division (MrD), was discovered at the caudal margin of the neostriatum. The MrD was shown to be involved in learning and memory in the rat. The aim of this study was to investigate the expression of the immediate-early genes c-fos and c-jun in the MrD of the striatum during learning and memory processes in the rat, immunocytochemical and Western blot methods were used to examine Y-maze trained rats.Methods The rats were divided into three groups, namely the training, pseudotraining, and control groups. After Y-maze training, the expression of the immediate-early genes c-fos and c-jun in the MrD of the rats was investigated using immunocytochemical and Western blot methods. Results After one hour of Y-maze training, the expression of c-jun and c-fos proteins was significantly enhanced in the MrD; the c-jun protein, in particular, was more intensely expressed in this region than in other parts of the striatum. The expression of these two proteins in the training group was significantly higher than in the pseudotraining and control groups. In addition, positive expression was also found in the hippocampus, cingulum cortex, thalamus, and in other areas. Western blot disclosed two immunoreactive bands for the anti-c-fos antibody (47 kD and 54 kD) and two immunoreactive bands for the anti-c-jun antibody (39 kD and 54 kD). Conclusions These results indicate that the immediate-early genes c-fos and c-jun participate in signal transduction during the learning and memory processes associated with Y-maze training in rats.

  8. Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion

    DEFF Research Database (Denmark)

    Lehrmann, E; Christensen, Thomas; Zimmer, J

    1997-01-01

    Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part of the striatum and adjacent neocortex, with selective neuronal necrosis in the bordering penumbral zones. Administration of glutamate, cytokine, and leukocyte antagonists have rescued mainly neocortical....../macrophages in the adjacent penumbra. Within the neocortex, a later onset of degeneration along the insular-parietal axis was marked by neuronal expression of heat shock protein and a progressive microglial activation with induction of the full repertoire of microglial activation markers, including a widespread microglial...

  9. Age-dependent changes in 24-hour rhythms of catecholamine content and turnover in hypothalamus, corpus striatum and pituitary gland of rats injected with Freund's adjuvant

    Directory of Open Access Journals (Sweden)

    Reyes Toso Carlos A

    2001-11-01

    Full Text Available Abstract Background Little information is available on the circadian sequela of an immune challenge in the brain of aged rats. To assess them, we studied 24-hour rhythms in hypothalamic and striatal norepinephrine (NE content, hypothalamic and striatal dopamine (DA turnover and hypophysial NE and DA content, in young (2 months and aged (18–20 months rats killed at 6 different time intervals, on day 18th after Freund's adjuvant or adjuvant's vehicle administration. Results Aging decreased anterior and medial hypothalamic NE content, medial and posterior hypothalamic DA turnover, and striatal NE concentration and DA turnover. Aging also decreased NE and DA content in pituitary neurointermediate lobe and augmented DA content in the anterior pituitary lobe. Immunization by Freund's adjuvant injection caused: (i reduction of DA turnover in anterior hypothalamus and corpus striatum; (ii acrophase delay of medial hypothalamic DA turnover in old rats, and of striatal NE content in young rats; (iii abolition of 24-h rhythm in NE and DA content of neurointermediate pituitary lobe, and in DA content of anterior lobe, of old rats. Conclusions The decline in catecholamine neurotransmission with aging could contribute to the decrease of gonadotropin and increase of prolactin release reported in similar groups of rats. Some circadian responses to immunization, e.g. suppression of 24-h rhythms of neurointermediate lobe NE and DA and of anterior lobe DA were seen only in aged rats.

  10. Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum.

    Science.gov (United States)

    Mingori, Moara Rodrigues; Heimfarth, Luana; Ferreira, Charles Francisco; Gomes, Henrique Mautone; Moresco, Karla Suzana; Delgado, Jeferson; Roncato, Sabrina; Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2017-08-01

    During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

  11. Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

    Science.gov (United States)

    Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

    2014-01-01

    Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

  12. Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats.

    Science.gov (United States)

    Saund, Jasjot; Dautan, Daniel; Rostron, Claire; Urcelay, Gonzalo P; Gerdjikov, Todor V

    2017-08-01

    Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control.

  13. [Effect of Corydalis Rhizoma and L-tetrahydropalmatine on dopamine system of hippocampus and striatum in morphine-induced conditioned place preference rats].

    Science.gov (United States)

    Yu, Shou-Yang; Bai, Wei-Feng; Tu, Ping; Qiu, Cheng-Kai; Yang, Pei-Run; Luo, Su-Yuan

    2016-10-01

    To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹). Models of CPP were validated in those psychological dependence rats after 48 h training. The dopamine contents were detected as soon as the materials of hippocampus and striatum are harvested from rats of NS control group and model group. The DAT and D2R levels are measured by Western blot. The high, medium and low dose group of Corydalis Rhizoma are given Corydalis Rhizoma 2, 1, 0.5 g•kg⁻¹ water extraction liquid respectively (which contains L-THP were 0.274, 0.137 and 0.137 mg respectively), and the high, medium and low dose group of L-THP were given L-THP 3.76, 1.88, 0.94 mg•kg⁻¹ lavage treatment respectively, NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP, again tested DA levels and expression of DAT and D2R similar to the front of materials. The reduction effects of CPP were observed in the groups of both Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) subjected to medicine for 6 days (Peffect of L-THP. The similar effects were observed on the neurotransmitter dopamine, DAT and D2R in learning and memory-related brain areas, hippocampus and striatum of the morphine- dependent rats. Copyright© by the Chinese Pharmaceutical Association.

  14. Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum.

    Science.gov (United States)

    Faro, Lilian R F; Ferreira Nunes, Brenda V; Alfonso, Miguel; Ferreira, Vania M; Durán, Rafael

    2013-09-15

    The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5. Administration of GLA to CNQX (500μM) pretreated animals produced an effect that was not significantly different from the one produced in animals not pretreated with CNQX. On the other hand, administration of GLA to l-NAME (100μM) or 7-NI (100μM) pretreated animals, produced increases in dopamine overflow that were ∼80% and ∼75% smaller than those observed in animals not pretreated with these inhibitors. In summary, GLA appears to act, at least in part, through an overstimulation of NMDA (and not AMPA/kainate) receptors with possible NO production to induce in vivo dopamine release. Administration of NMDA receptor antagonists and NOS inhibitors partially blocks the release of dopamine from rat striatum. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. 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.

  16. The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats.

    Science.gov (United States)

    Ahmed, Nawal A; Radwan, Nasr M; Aboul Ezz, Heba S; Salama, Noha A

    2017-01-01

    Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm 2 , SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain.

  17. The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine, and glutamate in the striatum of rats with altered function of VMAT2.

    Science.gov (United States)

    Gołembiowska, Krystyna; Dziubina, Anna

    2012-08-01

    It has been shown that a decreased vesicular monoamine transporter (VMAT2) function and the disruption of dopamine (DA) storage is an early contributor to oxidative damage of dopamine neurons in Parkinson's disease (PD). In our previous study, we demonstrated that adenosine A(2A) receptor antagonists suppressed oxidative stress in 6-hydroxydopamine-treated rats suggesting that this effect may account for neuroprotective properties of drugs. In the present study, rats were injected with reserpine (10 mg/kg sc) and 18 h later the effect of the adenosine A(2A) receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on extracellular DA, glutamate and hydroxyl radical formation was studied in the rat striatum using in vivo microdialysis. By disrupting VMAT2 function, reserpine depleted DA stores, and increased glutamate and hydroxyl radical levels in the rat striatum. CSC (1 mg/kg) but not ZM 241385 (3 mg/kg) increased extracellular DA level and production of hydroxyl radical in reserpinised rats. Both antagonists decreased the reserpine-induced increase in extracellular glutamate. L-3,4-Dihydroxyphenylalanine (L-DOPA) (25 mg/kg) significantly enhanced extracellular DA, had no effect on reserpine-induced hydroxyl radical production and decreased extracellular glutamate concentration. CSC but not ZM 241385 given jointly with L-DOPA increased the effect of L-DOPA on extracellular DA and augmented the reserpine-induced hydroxyl radical production. CSC and ZM 241385 did not influence extracellular glutamate level, which was decreased by L-DOPA. It seems that by decreasing the MAO-dependent DA metabolism rate, CSC raised cytosolic DA and by DA autoxidation, it induced hydroxyl radical overproduction. Thus, the methylxanthine A(2A) receptor antagonists bearing properties of MAO-B inhibitor, like CSC, may cause a risk of oxidative stress resulting from dysfunctional DA storage

  18. Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

    Directory of Open Access Journals (Sweden)

    Sara ePalm

    2014-07-01

    Full Text Available Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction.

  19. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  20. Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

    Science.gov (United States)

    Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

    2001-11-30

    , the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.

  1. Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

    Science.gov (United States)

    Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

    2018-03-15

    Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Butcher, S.P.; Lazarewicz, J.W.; Hamberger, A.

    1987-11-01

    The in vivo effects of kainate (1 mM) on fluxes of /sup 45/Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate /sup 45/Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate /sup 45/Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate-evoked alterations in either dialysate /sup 45/Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals.

  3. Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

    International Nuclear Information System (INIS)

    Opacka-Juffry, J.; Hume, S. P.; Ashworth, S.; Ahier, R. G.

    1997-01-01

    Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetized rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100 mg/kg i.p.) resulted in an increase in [ 11 C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitization was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg), extracellular GABA levels were reduced by ∼20 % in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease. (author)

  4. Cocaine modulates allosteric D2-σ1 receptor-receptor interactions on dopamine and glutamate nerve terminals from rat striatum.

    Science.gov (United States)

    Beggiato, Sarah; Borelli, Andrea Celeste; Borroto-Escuela, Dasiel; Corbucci, Ilaria; Tomasini, Maria Cristina; Marti, Matteo; Antonelli, Tiziana; Tanganelli, Sergio; Fuxe, Kjell; Ferraro, Luca

    2017-12-01

    The effects of nanomolar cocaine concentrations, possibly not blocking the dopamine transporter activity, on striatal D 2 -σ 1 heteroreceptor complexes and their inhibitory signaling over Gi/o, have been tested in rat striatal synaptosomes and HEK293T cells. Furthermore, the possible role of σ 1 receptors (σ 1 Rs) in the cocaine-provoked amplification of D 2 receptor (D 2 R)-induced reduction of K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes, has also been investigated. The dopamine D 2 -likeR agonist quinpirole (10nM-1μM), concentration-dependently reduced K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes. The σ 1 R antagonist BD1063 (100nM), amplified the effects of quinpirole (10 and 100nM) on K + -evoked [ 3 H]-DA, but not glutamate, release. Nanomolar cocaine concentrations significantly enhanced the quinpirole (100nM)-induced decrease of K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes. In the presence of BD1063 (10nM), cocaine failed to amplify the quinpirole (100nM)-induced effects. In cotransfected σ 1 R and D 2L R HEK293T cells, quinpirole had a reduced potency to inhibit the CREB signal versus D 2L R singly transfected cells. In the presence of cocaine (100nM), the potency of quinpirole to inhibit the CREB signal was restored. In D 2L singly transfected cells cocaine (100nM and 10μM) exerted no modulatory effects on the inhibitory potency of quinpirole to bring down the CREB signal. These results led us to hypothesize the existence of functional D 2 -σ 1 R complexes on the rat striatal DA and glutamate nerve terminals and functional D 2 -σ 1 R-DA transporter complexes on the striatal DA terminals. Nanomolar cocaine concentrations appear to alter the allosteric receptor-receptor interactions in such complexes leading to enhancement of Gi/o mediated D 2 R signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

    2014-07-15

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

    Science.gov (United States)

    Tamakoshi, Keigo; Ishida, Kazuto; Kawanaka, Kentaro; Takamatsu, Yasuyuki; Tamaki, Hiroyuki

    2017-10-01

    We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Irradiation inactivation studies of the dopamine D1 receptor and dopamine-stimulated adenylate cyclase in rat striatum

    International Nuclear Information System (INIS)

    Anderson, P.H.; Nielson, M.

    1987-01-01

    In frozen rat striatal tissue, exposed to 10 MeV electrons from a linear accelerator, the sizes of the dopamine (DA) D 1 receptor and the DA sensitive adenylate cyclase complex were determined using target size analysis. The number of D 1 receptors (labelled by [ 3 H]SCH 23390)declined monoexponentially with increasing radiation intensity, yielding a molecular weight (mol. wt.) of 80kDa. Also the activity of the catalytic unit (C) of the adenylate cyclase (as measured by forskolin stimulation), decreased monoexponentially however with a mol. wt. of 145 kDa. Both basal, DA- and flouride (F - ) stimulated activity declined in a concave downward fashion with a limiting mol. wt. of 134, 138 and 228 kDa respectively. It was estimated that the basal and DA - stimulated activity originated from an enzyme complex with a mol. wt. of 325 kDa a value close to the combined size of R G S + C. These data suggest that F - stimulation of the adenylate cyclase, which occurs by a G S activation, does not cause disassociation of G S into the α S and βγ subunits. Further, the AA-regulated adenylate cyclase apparently exists as a complex consisting of RG S and C; the mechanisms of hormonal activation is dissociation of C from this complex

  8. Distinct presynaptic regulation of dopamine release through NMDA receptors in striosome- and matrix-enriched areas of the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Krebs, M.O.; Trovero, F.; Desban, M.; Gauchy, C.; Glowinski, J.; Kemel, M.L. (College de France, Paris (France))

    1991-05-01

    Striosome- and matrix-enriched striatal zones were defined in coronal and sagittal brain sections of the rat, on the basis of {sup 3}H-naloxone binding to mu-opiate receptors (a striosome-specific marker). Then, using a new in vitro microsuperfusion device, the NMDA (50 microM)-evoked release of newly synthesized {sup 3}H-dopamine ({sup 3}H-DA) was examined in these four striatal areas under Mg(2+)-free conditions. The amplitudes of the responses were different in striosomal (171 +/- 6% and 161 +/- 5% of the spontaneous release) than in matrix areas (223 +/- 6% and 248 +/- 12%), even when glycine (1 or 100 microM) was coapplied (in the presence of 1 microM strychnine). In the four areas, the NMDA-evoked release of {sup 3}H-DA was blocked completely by Mg{sup 2}{sup +} (1 mM) or (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801; 1 microM) and almost totally abolished by kynurenate (100 microM). Because the tetrodotoxin (TTX)-resistant NMDA-evoked release of {sup 3}H-DA was similar in striosome- (148 +/- 5% and 152 +/- 6%) or matrix-enriched (161 +/- 5% and 156 +/- 7%) areas, the indirect (TTX-sensitive) component of NMDA-evoked responses, which involves striatal neurons and/or afferent fibers, seems more important in the matrix- than in the striosome-enriched areas. The modulation of DA release by cortical glutamate and/or aspartate-containing inputs through NMDA receptors in the matrix appears thus to be partly distinct from that observed in the striosomes, providing some functional basis for the histochemical striatal heterogeneity.

  9. Dynorphin/KOP and nociceptin/NOP gene expression and epigenetic changes by cocaine in rat striatum and nucleus accumbens.

    Science.gov (United States)

    Caputi, Francesca Felicia; Di Benedetto, Manuela; Carretta, Donatella; Bastias del Carmen Candia, Sussy; D'Addario, Claudio; Cavina, Chiara; Candeletti, Sanzio; Romualdi, Patrizia

    2014-03-03

    Cocaine induces neurochemical changes of endogenous prodynorphin-kappa opioid receptor (pDYN-KOP) and pronociceptin/orphaninFQ-nociceptin receptor (pN/OFQ-NOP) systems. Both systems play an important role in rewarding mechanisms and addictive stimulus processing by modulating drug-induced dopaminergic activation in the mesocortico-limbic brain areas. They are also involved in regulating stress mechanisms related to addiction. The aim of this study was to investigate possible changes of gene expression of the dynorphinergic and nociceptinergic system components in the nucleus accumbens (NA) and in medial and lateral caudate putamen (mCPu and lCPu, respectively) of rats, following chronic subcutaneous infusion of cocaine. In addition, the epigenetic histone modifications H3K4me3 and H3K27me3 (an activating and a repressive marker, respectively) at the promoter level of the pDYN, KOP, pN/OFQ and NOP genes were investigated. Results showed that cocaine induced pDYN gene expression up-regulation in the NA and lCPu, and its down-regulation in the mCPu, whereas KOP mRNA levels were unchanged. Moreover, cocaine exposure decreased pN/OFQ gene expression in the NA and lCPu, while NOP mRNA levels appeared significantly increased in the NA and decreased in the lCPu. Specific changes of the H3K4me3 and H3K27me3 levels were found at pDYN, pN/OFQ, and NOP gene promoter, consistent with the observed gene expression alterations. The present findings contribute to better define the role of endogenous pDYN-KOP and pN/OFQ-NOP systems in neuroplasticity mechanisms following chronic cocaine treatment. The epigenetic histone modifications underlying the gene expression changes likely mediate the effects of cocaine on transcriptional regulation of specific gene promoters that result in long-lasting drug-induced plasticity. © 2013.

  10. Dopamine transporter binding in rat striatum: a comparison of [O-methyl-{sup 11}C]{beta}-CFT and [N-methyl-{sup 11}C]{beta}-CFT

    Energy Technology Data Exchange (ETDEWEB)

    Yoder, Karmen K.; Hutchins, Gary D.; Mock, Bruce H.; Fei, Xiangshu; Winkle, Wendy L. [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States); Gitter, Bruce D.; Territo, Paul R. [Lilly Center for Anatomical and Molecular Imaging, Integrative Biology Division, Lilly Research Laboratories, Greenfield, IN 46140 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2009-01-15

    Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [{sup 11}C]{beta}-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [{sup 11}C]{beta}-CFT is commonly labeled at the N-methyl position. However, labeling of [{sup 11}C]{beta}-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [{sup 11}C]{beta}-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-{sup 11}C]{beta}-CFT and once with [O-methyl-{sup 11}C]{beta}-CFT. DAT binding potentials (BP{identical_to}B'{sub avail}/K{sub d}) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-{sup 11}C]{beta}-CFT and [O-methyl-{sup 11}C]{beta}-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258{+-}30 GBq/{mu}mol. Average BP values for right and left striata with [N-methyl-{sup 11}C]{beta}-CFT were 1.16{+-}0.08 and 1.23{+-}0.14, respectively. BP values for [O-methyl-{sup 11}C]{beta}-CFT were 1.18{+-}0.08 (right) and 1.22{+-}0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-{sup 11}C]{beta}-CFT is quantitatively equivalent to [N-methyl-{sup 11}C]{beta}-CFT in the rat striatum.

  11. c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats.

    Science.gov (United States)

    Dela Cruz, J A D; Coke, T; Karagiorgis, T; Sampson, C; Icaza-Cukali, D; Kest, K; Ranaldi, R; Bodnar, R J

    2015-02-01

    Overconsumption of nutrients high in fats and sugars can lead to obesity. Previous studies indicate that sugar or fat consumption activate individual brain sites using Fos-like immunoreactivity (FLI). Sugars and fats also elicit conditioned flavor preferences (CFP) that are differentially mediated by flavor-flavor (orosensory: f/f) and flavor-nutrient (post-ingestive: f/n) processes. Dopamine (DA) signaling in the medial prefrontal cortex (mPFC), the amygdala (AMY) and the nucleus accumbens (NAc), has been implicated in acquisition and expression of fat- and sugar-CFP. The present study examined the effects of acute consumption of fat (corn oil: f/f and f/n), glucose (f/f and f/n), fructose, (f/f only), saccharin, xanthan gum or water upon simultaneous FLI activation of DA mesotelencephalic nuclei (ventral tegmental area (VTA)) and projections (infralimbic and prelimbic mPFC, basolateral and central-cortico-medial AMY, core and shell of NAc as well as the dorsal striatum). Consumption of corn oil solutions, isocaloric to glucose and fructose, significantly increased FLI in all sites except for the NAc shell. Glucose intake significantly increased FLI in both AMY areas, dorsal striatum and NAc core, but not in either mPFC area, VTA or Nac shell. Correspondingly, fructose intake significantly increased FLI in the both AMY areas, the infralimbic mPFC and dorsal striatum, but not the prelimbic mPFC, VTA or either NAc area. Saccharin and xanthan gum intake failed to activate FLI relative to water. When significant FLI activation occurred, highly positive relationships were observed among sites, supporting the idea of activation of a distributed brain network mediating sugar and fat intake. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  13. Basketball training increases striatum volume.

    Science.gov (United States)

    Park, In Sung; Lee, Kea Joo; Han, Jong Woo; Lee, Nam Joon; Lee, Won Teak; Park, Kyung Ah; Rhyu, Im Joo

    2011-02-01

    The striatum is associated with the learning and retention of motor skills. Several studies have shown that motor learning induces neuronal changes in the striatum. We investigated whether macroscopic change in striatum volume occurs in a segment of the human population who learned basketball-related motor skills and practiced them throughout their entire athletic life. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players and healthy controls, and striatum volumes were compared based on basketball proficiency, region and side. We identified morphological enlargement in the striatum of basketball players in comparison with controls. Our results suggest that continued practice and repetitive performance of basketball-related motor skills may induce plastic structural changes in the human striatum. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Representation of the body in the lateral striatum of the freely moving rat: Fast Spiking Interneurons respond to stimulation of individual body parts.

    Science.gov (United States)

    Kulik, Julianna M; Pawlak, Anthony P; Kalkat, Manraj; Coffey, Kevin R; West, Mark O

    2017-02-15

    Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input

  15. MDMA-evoked changes in the binding of dopamine D(2) receptor ligands in striatum of rats with unilateral serotonin depletion

    DEFF Research Database (Denmark)

    Ostergaard, Søren Dinesen; Alstrup, Aage Kristian Olsen; Gramsbergen, Jan Bert

    2010-01-01

    We earlier reported an anomalous 50% decrease in [(11)C]N-methylspiperone ([(11)C]NMSP) binding to dopamine D(2)-like receptors in living pig striatum after challenge with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), suggesting either (1) a species peculiarity in the vulnerability...... lesions, later verified by [(125)I]RTI-55 autoradiography. Baseline [(11)C]NMSP microPET recordings were followed by either saline or MDMA-HCl (4 mg/kg) injections (i.v.), and a second [(11)C]NMSP recording, culminating with injection of [(3)H]raclopride for autoradiography ex vivo. Neither MDMA......-challenge nor serotonin lesion had any detectable effect on [(11)C]NMSP binding. In contrast, MDMA challenge increased receptor occupancy by [(3)H]raclopride ex vivo (relative to the B(max) in vitro) from 8% to 12%, and doubled the free ligand concentration in cerebral cortex, apparently by blocking hepatic CYP...

  16. Vomeronasal inputs to the rodent ventral striatum.

    Science.gov (United States)

    Ubeda-Bañon, I; Novejarque, A; Mohedano-Moriano, A; Pro-Sistiaga, P; Insausti, R; Martinez-Garcia, F; Lanuza, E; Martinez-Marcos, A

    2008-03-18

    Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.

  17. Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.

    Science.gov (United States)

    Yu-Taeger, Libo; Bonin, Michael; Stricker-Shaver, Janice; Riess, Olaf; Nguyen, Hoa Huu Phuc

    2017-05-01

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p < 0.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum. Evidence that [3H]dopamine can label a high affinity agonist-binding state of the D1 dopamine receptor

    International Nuclear Information System (INIS)

    Leff, S.E.; Creese, I.

    1985-01-01

    The interactions of dopaminergic agonists and antagonists with 3 H-agonist labeled D3 dopaminergic binding sites of rat striatum have been characterized by radioligand-binding techniques. When the binding of [ 3 H]dopamine and [ 3 H]apomorphine to D2 dopamine receptors is blocked by the inclusion of D2 selective concentrations of unlabeled spiroperidol or domperidone, these ligands appear to label selectively the previously termed D3 binding site. Antagonist/[ 3 H]dopamine competition curves are of uniformly steep slope (nH . 1.0), suggesting the presence of a single D3 binding site. The relative potencies of antagonists to inhibit D3 specific [ 3 H]dopamine binding are significantly correlated with their potencies to block D1 dopamine receptors as measured by the inhibition of both dopamine-stimulated adenylate cyclase and [ 3 H]flupentixol-binding activities. The affinities of agonists to inhibit D3 specific [ 3 H]dopamine binding are also correlated with estimates of these agonists affinities for the high affinity binding component of agonist/[ 3 H]flupentixol competition curves. Both D3 specific [ 3 H] dopamine binding and the high affinity agonist-binding component of dopamine/[ 3 H]flupentixol competition curves show a similar sensitivity to guanine nucleotides. Taken together, these data strongly suggest that the D3 binding site is related to a high affinity agonist-binding state of the D1 dopamine receptor

  19. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, R H; Ingvar, M; Lindvall, O; Stenevi, U; Bjoerklund, A

    1982-03-01

    Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by (14C)deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. Overall the results indicate that behaviorally functional neuronal grafts spontaneously metabolize dopamine and utilize glucose at rates characteristic of the intact nigrostriatal system. This provides further evidence that ectopic intracortical nigral transplants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6-hydroxydopamine lesion.

  20. Identification of D3 and sigma receptors in the rat striatum and nucleus accumbens using (+/-)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin and carbetapentane.

    Science.gov (United States)

    Wallace, D R; Booze, R M

    1995-02-01

    Cross-reactions between dopamine D3 and sigma receptor ligands were investigated using (+/-)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin [(+/-)-7-OH-[3H]-DPAT], a putative D3-selective radioligand, in conjunction with the unlabeled sigma ligands 1,3-di(2-tolyl)guanidine (DTG), carbetapentane, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane [R(-)-PPAP]. In transfected CCL1.3 mouse fibroblasts expressing the human D3 receptor, neither DTG nor carbetapentane (0.1 microM) displaced (+/-)-7-OH-[3H]DPAT binding. R(-)-PPAP (0.1 microM) displaced 39.6 +/- 1.0% of total (+/-)-7-OH-[3H]DPAT binding. In striatal and nucleus accumbens homogenates, (+/-)-7-OH-[3H]DPAT labeled a single site (15-20 fmol/mg of protein) with high (1 nM) affinity. Competition analysis with carbetapentane defined both high- and low-affinity sites in striatal (35 and 65%, respectively) and nucleus accumbens (59 and 41%, respectively) tissue, yet R(-)-PPAP identified two sites in equal proportion. Carbetapentane and R(-)-PPAP (0.1 microM) displaced approximately 20-50% of total (+/-)-7-OH-[3H]DPAT binding in striatum, nucleus accumbens, and olfactory tubercle in autoradiographic studies, with the nucleus accumbens shell subregion exhibiting the greatest displacement. To determine directly (+)-7-OH-[3H]DPAT binding to sigma receptors, saturation analysis was performed in the cerebellum while masking D3 receptors with 1 microM dopamine. Under these conditions (+)-7-OH-[3H]DPAT labeled sigma receptors with an affinity of 24 nM. These results suggest that (a) (+/-)-7-OH-[3H]DPAT binds D3 receptors with high affinity in rat brain and (b) a significant proportion of (+/-)-7-OH-[3H]DPAT binding consists of sigma 1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.

  1. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    Science.gov (United States)

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

    2016-05-01

    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  2. Further studies on the nature of postsynaptic dopamine uptake and metabolism in rat striatum: sodium dependency and investigation of a possible role for carrier-mediated uptake into serotonin neurons

    Energy Technology Data Exchange (ETDEWEB)

    Schoepp, D.D.; Azzaro, A.J.

    1985-06-01

    The nature of postsynaptic sites involved in the uptake and metabolism of striatal 3,4-dihydroxyphenylethylamine (dopamine, DA) was investigated. The accumulation of (/sup 3/H)DA (10(-7) M) into slices of rat striatum was found to be greatly dependent on the presence of sodium ion in the incubation medium. However, the formation of the (/sup 3/H)dihydroxyphenylacetic acid (DOPAC) and (/sup 3/H)homovanillic acid (HVA) was only partially reduced in the absence of sodium. Inhibition of carrier-mediated DA neuronal uptake with nomifensine significantly decreased DA accumulation (18% of control) and (/sup 3/H)DOPAC formation (62% of control), but enhanced (/sup 3/H)HVA production (143% of control). Inhibition of the 5-hydroxytryptamine (5-HT, serotonin) neuronal uptake system with fluoxetine (10(-6) M) or selective 5-HT neuronal lesions with 5,7-dihydroxytryptamine (5,7-DHT) had no effect on (/sup 3/H)DOPAC or (/sup 3/H)HVA formed from (/sup 3/H)DA in the presence or absence of nomifensine. These results demonstrate that the uptake and subsequent metabolism of striatal DA to DOPAC and HVA is only partially dependent on carrier-mediated uptake mechanism(s) requiring sodium ion. These data support our previous findings suggesting a significant role for synaptic glial cell deamination and O-methylation of striatal DA. Further, experiments with fluoxetine or 5,7-DHT suggest that 5-HT neurons do not significantly contribute in the synaptic uptake and metabolism of striatal DA.

  3. Selective labelling of dopamine (D2) receptors in rat striatum by [3H]domperidone but not by [3H]spiperone

    International Nuclear Information System (INIS)

    Lazareno, S.; Nahorski, S.R.

    1982-01-01

    Specific binding of [ 3 H]spiperone and [ 3 H]domperidone, displaceable by 1 μM d-butaclamol, was examined in rat striatal membranes. Initial saturation and displacement experiments indicated that [ 3 H]spiperone bound to more sites than [ 3 H]domperidone and that, whilst all displacing drugs were more potent against [ 3 H]domperidone, this difference in potency was greatest for dopamine agonists and specific antagonists and least for 5HT-related drugs. Sulpiride displaced [ 3 H]spiperone biphasically, and was used at a concentration of 50 μM to examine two classes of [ 3 H]spiperone binding: site 1 displaceable by sulpiride, and site 2 displaceable by butaclamol but not by sulpiride. Site 1 had twice the capacity of site 2 and ten times the affinity for [ 3 H]spiperone. Dopaminergic drugs displaced preferentially from site 1, whilst 5HT-related drugs were more potent against site 2. GTP reduced the potency of dopamine, noradrenaline and, to a lesser extent, 5HT at site 1, but had no effect at site 2. [ 3 H]Domperidone sites had the same capacity as [ 3 H]spiperone site 1, and dopamine, noradrenaline and 5HT, in the absence or presence of GTP, and sulpiride had essentially identical affinities for [ 3 H]domperidone sites and [ 3 H]spiperone site 1. It is concluded that [ 3 H]domperidone and [ 3 H]spiperone label an identical population of dopamine (D 2 ) receptors, whilst [ 3 H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5TH-related. [ 3 H]Domperidone is the better radioligand for dopamine receptors. (Auth.)

  4. Learning and motivation in the human striatum.

    Science.gov (United States)

    Shohamy, Daphna

    2011-06-01

    The past decade has seen a dramatic change in our understanding of the role of the striatum in behavior. Early perspectives emphasized a role for the striatum in habitual learning of stimulus-response associations and sequences of actions. Recent advances from human neuroimaging research suggest a broader role for the striatum in motivated learning. New findings demonstrate that the striatum represents multiple learning signals and highlight the contribution of the striatum across many cognitive domains and contexts. Recent findings also emphasize interactions between the striatum and other specialized brain systems for learning. Together, these findings suggest that the striatum contributes to a distributed network that learns to select actions based on their predicted value in order to optimize behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  6. PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

    Directory of Open Access Journals (Sweden)

    G. R. Hassanzadeh G. Behzadi

    2007-08-01

    Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

  7. Re-thinking the role of the dorsal striatum in egocentric/response strategy.

    Science.gov (United States)

    Botreau, Fanny; Gisquet-Verrier, Pascale

    2010-01-01

    Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

  8. Habit formation coincides with shifts in reinforcement representations in the sensorimotor striatum.

    Science.gov (United States)

    Smith, Kyle S; Graybiel, Ann M

    2016-03-01

    Evaluating outcomes of behavior is a central function of the striatum. In circuits engaging the dorsomedial striatum, sensitivity to goal value is accentuated during learning, whereas outcome sensitivity is thought to be minimal in the dorsolateral striatum and its habit-related corticostriatal circuits. However, a distinct population of projection neurons in the dorsolateral striatum exhibits selective sensitivity to rewards. Here, we evaluated the outcome-related signaling in such neurons as rats performed an instructional T-maze task for two rewards. As the rats formed maze-running habits and then changed behavior after reward devaluation, we detected outcome-related spike activity in 116 units out of 1,479 recorded units. During initial training, nearly equal numbers of these units fired preferentially either after rewarded runs or after unrewarded runs, and the majority were responsive at only one of two reward locations. With overtraining, as habits formed, firing in nonrewarded trials almost disappeared, and reward-specific firing declined. Thus error-related signaling was lost, and reward signaling became generalized. Following reward devaluation, in an extinction test, postgoal activity was nearly undetectable, despite accurate running. Strikingly, when rewards were then returned, postgoal activity reappeared and recapitulated the original early response pattern, with nearly equal numbers responding to rewarded and unrewarded runs and to single rewards. These findings demonstrate that outcome evaluation in the dorsolateral striatum is highly plastic and tracks stages of behavioral exploration and exploitation. These signals could be a new target for understanding compulsive behaviors that involve changes to dorsal striatum function. Copyright © 2016 the American Physiological Society.

  9. Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

    Science.gov (United States)

    Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

    2007-11-01

    Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

  10. The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

    Science.gov (United States)

    Cole, Sindy; Stone, Andrew D; Petrovich, Gorica D

    2017-12-01

    The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning. Rats with DMS lesions selectively attenuated responding to a food cue but not a control cue, early in training, suggesting the DMS is involved when initial associations are formed. Similarly, initial reversal learning was attenuated in rats with DMS lesions, which suggests impaired flexibility to adjust behavior when the cue meaning is reversed. We also examined the effect of DMS lesions on food intake during tests with access to a highly palatable food along with standard chow diet. Rats with DMS lesions showed an altered pattern of intake, with an initial reduction in high-fat diet followed by an increase in chow consumption. These results demonstrate that the DMS has a role in mediating cue-food learning and its subsequent reversal, as well as changes in food intake when a choice is provided. Together, these results demonstrate the DMS is involved in reward associative learning and reward consumption, when behavioral flexibility is needed to adjust responding or consumption to match the current value. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Pulvinar projections to the striatum and amygdala

    Directory of Open Access Journals (Sweden)

    Jonathan D Day-Brown

    2010-11-01

    Full Text Available Visually-guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as blindsight. Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri, a species considered to be a protypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd and central (Pc pulvinar both receive topographic (specific projections from SC, and Pd receives an additional nontopographic (diffuse projection from SC (Chomsung et al., 2008; JCN 510:24-46. Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP and parvalbumin (PV to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvinostriatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: 1 topographic visual information from SC to striatum to aid in guiding precise movements, and 2 nontopographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

  12. Extensive training and hippocampus or striatum lesions: effect on place and response strategies.

    Science.gov (United States)

    Jacobson, Tara K; Gruenbaum, Benjamin F; Markus, Etan J

    2012-02-01

    The hippocampus has been linked to spatial navigation and the striatum to response learning. The current study focuses on how these brain regions continue to interact when an animal is very familiar with the task and the environment and must continuously switch between navigation strategies. Rats were trained to solve a plus maze using a place or a response strategy on different trials within a testing session. A room cue (illumination) was used to indicate which strategy should be used on a given trial. After extensive training, animals underwent dorsal hippocampus, dorsal lateral striatum or sham lesions. As expected hippocampal lesions predominantly caused impairment on place but not response trials. Striatal lesions increased errors on both place and response trials. Competition between systems was assessed by determining error type. Pre-lesion and sham animals primarily made errors to arms associated with the wrong (alternative) strategy, this was not found after lesions. The data suggest a qualitative change in the relationship between hippocampal and striatal systems as a task is well learned. During acquisition the two systems work in parallel, competing with each other. After task acquisition, the two systems become more integrated and interdependent. The fact that with extensive training (as something becomes a "habit"), behaviors become dependent upon the dorsal lateral striatum has been previously shown. The current findings indicate that dorsal lateral striatum involvement occurs even when the behavior is spatial and continues to require hippocampal processing. Published by Elsevier Inc.

  13. Reward-modulated motor information in identified striatum neurons.

    Science.gov (United States)

    Isomura, Yoshikazu; Takekawa, Takashi; Harukuni, Rie; Handa, Takashi; Aizawa, Hidenori; Takada, Masahiko; Fukai, Tomoki

    2013-06-19

    It is widely accepted that dorsal striatum neurons participate in either the direct pathway (expressing dopamine D1 receptors) or the indirect pathway (expressing D2 receptors), controlling voluntary movements in an antagonistically balancing manner. The D1- and D2-expressing neurons are activated and inactivated, respectively, by dopamine released from substantia nigra neurons encoding reward expectation. However, little is known about the functional representation of motor information and its reward modulation in individual striatal neurons constituting the two pathways. In this study, we juxtacellularly recorded the spike activity of single neurons in the dorsolateral striatum of rats performing voluntary forelimb movement in a reward-predictable condition. Some of these neurons were identified morphologically by a combination of juxtacellular visualization and in situ hybridization for D1 mRNA. We found that the striatal neurons exhibited distinct functional activations before and during the forelimb movement, regardless of the expression of D1 mRNA. They were often positively, but rarely negatively, modulated by expecting a reward for the correct motor response. The positive reward modulation was independent of behavioral differences in motor performance. In contrast, regular-spiking and fast-spiking neurons in any layers of the motor cortex displayed only minor and unbiased reward modulation of their functional activation in relation to the execution of forelimb movement. Our results suggest that the direct and indirect pathway neurons cooperatively rather than antagonistically contribute to spatiotemporal control of voluntary movements, and that motor information is subcortically integrated with reward information through dopaminergic and other signals in the skeletomotor loop of the basal ganglia.

  14. Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Rivelilson Mendes de Freitas

    2003-06-01

    Full Text Available Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.. Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.. Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and

  15. Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

    2010-08-01

    Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

  16. Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze

    Science.gov (United States)

    Gardner, Robert S.; Suarez, Daniel F.; Robinson-Burton, Nadira K.; Rudnicky, Christopher J.; Gulati, Asish; Ascoli, Giorgio A.; Dumas, Theodore C.

    2016-01-01

    The strategies utilized to effectively perform a given task change with practice and experience. During a spatial navigation task, with relatively little training, performance is typically attentive enabling an individual to locate the position of a goal by relying on spatial landmarks. These (place) strategies require an intact hippocampus. With task repetition, performance becomes automatic; the same goal is reached using a fixed response or sequence of actions. These (response) strategies require an intact striatum. The current work aims to understand the activation patterns across these neural structures during this experience-dependent strategy transition. This was accomplished by region-specific measurement of activity-dependent immediate early gene expression among rats trained to different degrees on a dual-solution task (i.e., a task that can be solved using either place or response navigation). As expected, rats increased their reliance on response navigation with extended task experience. In addition, dorsal hippocampal expression of the immediate early gene Arc was considerably reduced in rats that used a response strategy late in training (as compared with hippocampal expression in rats that used a place strategy early in training). In line with these data, vicarious trial and error, a behavior linked to hippocampal function, also decreased with task repetition. Although Arc mRNA expression in dorsal medial or lateral striatum alone did not correlate with training stage, the ratio of expression in the medial striatum to that in the lateral striatum was relatively high among rats that used a place strategy early in training as compared with the ratio among over-trained response rats. Altogether, these results identify specific changes in the activation of dissociated neural systems that may underlie the experience-dependent emergence of response-based automatic navigation. PMID:26976088

  17. Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

    Science.gov (United States)

    2016-01-01

    The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate

  18. Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

    Science.gov (United States)

    Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W

    2012-06-20

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

  19. Urethritis due to corynebacterium striatum: An emerging germ.

    Science.gov (United States)

    Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

    2015-01-01

    Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

  20. Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

    Science.gov (United States)

    Xue, Bing; Chen, Elton C; He, Nan; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2017-01-01

    Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Separate populations of neurons in ventral striatum encode value and motivation.

    Science.gov (United States)

    Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

    2013-01-01

    Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  2. The influence of cannabinoids on learning and memory processes of the dorsal striatum.

    Science.gov (United States)

    Goodman, Jarid; Packard, Mark G

    2015-11-01

    Extensive evidence indicates that the mammalian endocannabinoid system plays an integral role in learning and memory. Our understanding of how cannabinoids influence memory comes predominantly from studies examining cognitive and emotional memory systems mediated by the hippocampus and amygdala, respectively. However, recent evidence suggests that cannabinoids also affect habit or stimulus-response (S-R) memory mediated by the dorsal striatum. Studies implementing a variety of maze tasks in rats indicate that systemic or intra-dorsolateral striatum infusions of cannabinoid receptor agonists or antagonists impair habit memory. In mice, cannabinoid 1 (CB1) receptor knockdown can enhance or impair habit formation, whereas Δ(9)THC tolerance enhances habit formation. Studies in human cannabis users also suggest an enhancement of S-R/habit memory. A tentative conclusion based on the available data is that acute disruption of the endocannabinoid system with either agonists or antagonists impairs, whereas chronic cannabinoid exposure enhances, dorsal striatum-dependent S-R/habit memory. CB1 receptors are required for multiple forms of striatal synaptic plasticity implicated in memory, including short-term and long-term depression. Interactions with the hippocampus-dependent memory system may also have a role in some of the observed effects of cannabinoids on habit memory. The impairing effect often observed with acute cannabinoid administration argues for cannabinoid-based treatments for human psychopathologies associated with a dysfunctional habit memory system (e.g. post-traumatic stress disorder and drug addiction/relapse). In addition, the enhancing effect of repeated cannabinoid exposure on habit memory suggests a novel neurobehavioral mechanism for marijuana addiction involving the dorsal striatum-dependent memory system. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  4. Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

    Science.gov (United States)

    Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

    2015-12-01

    Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum.

    Science.gov (United States)

    Taylor, S B; Anglin, J M; Paode, P R; Riggert, A G; Olive, M F; Conrad, C D

    2014-11-07

    Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after 2 weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Dopamine release in ventral striatum of pathological gamblers losing money

    DEFF Research Database (Denmark)

    Linnet, J; Peterson, E; Doudet, D J

    2010-01-01

    Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

  7. Inputs to the dorsal striatum of the mouse conserve the parallel circuit architecture of the forebrain

    Directory of Open Access Journals (Sweden)

    Weixing X Pan

    2010-12-01

    Full Text Available The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and, manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

  8. Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain.

    Science.gov (United States)

    Pan, Weixing X; Mao, Tianyi; Dudman, Joshua T

    2010-01-01

    The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

  9. Functional connectivity of the dorsal striatum in female musicians

    Directory of Open Access Journals (Sweden)

    Shoji eTanaka

    2016-04-01

    Full Text Available The dorsal striatum (caudate/putamen is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians.Resting state functional magnetic resonance imaging (fMRI data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to graph theoretical analysis and functional connectivity analysis. The graph theoretical analysis of the entire brain revealed that the degree, which represents the number of connections, of the bilateral putamen was significantly lower in musicians than in nonmusicians. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum and between the left caudate nucleus and cerebellum. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum, with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers. To the best of our knowledge, this is the first study suggesting that long-term musical training results in a less extensive or selective functional network of the dorsal striatum.

  10. Altered structural covariance of the striatum in functional dyspepsia patients.

    Science.gov (United States)

    Liu, P; Zeng, F; Yang, F; Wang, J; Liu, X; Wang, Q; Zhou, G; Zhang, D; Zhu, M; Zhao, R; Wang, A; Gong, Q; Liang, F

    2014-08-01

    Functional dyspepsia (FD) is thought to be involved in dysregulation within the brain-gut axis. Recently, altered striatum activation has been reported in patients with FD. However, the gray matter (GM) volumes in the striatum and structural covariance patterns of this area are rarely explored. The purpose of this study was to examine the GM volumes and structural covariance patterns of the striatum between FD patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 FD patients and 39 HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes in the two groups. The caudate- or putamen-related regions identified from VBM analysis were then used as seeds to map the whole brain voxel-wise structural covariance patterns. Finally, a correlation analysis was used to investigate the effects of FD symptoms on the striatum. The results showed increased GM volumes in the bilateral putamen and right caudate. Compared with the structural covariance patterns of the HCs, the FD-related differences were mainly located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus, lingual gyrus, and cerebellum. And significant positive correlations were found between the volumes in the striatum and the FD duration in the patients. These findings provided preliminary evidence for GM changes in the striatum and different structural covariance patterns in patients with FD. The current results might expand our understanding of the pathophysiology of FD. © 2014 John Wiley & Sons Ltd.

  11. Neuroimaging Studies Of Striatum In Cognition, Part I: Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Jean-Sebastien eProvost

    2015-10-01

    Full Text Available The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.

  12. CB1 cannabinoid receptor expression in the striatum: Association with corticostriatal circuits and developmental regulation

    Directory of Open Access Journals (Sweden)

    Vincent eVan Waes

    2012-03-01

    Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

  13. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  14. The dorsal striatum and ventral striatum play different roles in the programming of social behaviour: a tribute to Lex Cools.

    Science.gov (United States)

    van den Bos, Ruud

    2015-02-01

    Early work by Lex Cools suggested that the caudate nucleus (dorsal striatum) plays a role in programming social behaviour: enhanced activity in the caudate nucleus increased the extent to which ongoing behaviour is controlled by the individual's own behaviour (internal control) rather than by that of its partners (external control). Interestingly, later studies by others have indicated that the ventral striatum plays a role in external rather than internal control. Here, I discuss the role of these different striatal areas - and the emotional (ventral striatum) and cognitive control (dorsal striatum) system in which they are embedded - in the organization of social behaviour in the context of locus of control. Following on from this discussion, I will pay particular attention to individual differences in social behaviour (individuals with more internal or external control), focusing on the role of dopamine, serotonin and the effects of stress-related challenges in relation to their different position in a dominance hierarchy. I will subsequently allude to potential psychological and behavioural problems in the social domain following on from these differences in locus of control ['social obliviousness' (dorsal stratum) and 'social impulsivity' (ventral striatum)]. In doing so, I provide as a tribute a historical account of the early research by Lex Cools.

  15. Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

    Science.gov (United States)

    Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

    1995-12-01

    Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

  16. Neurochemical characterization of the tree shrew dorsal striatum

    Directory of Open Access Journals (Sweden)

    MATTHEW W RICE

    2011-08-01

    Full Text Available The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington's, Tourette's syndrome, obsessive-compulsive disorders and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei, which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase and acetylcholinesterase immunohistochemistry, and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum.

  17. Striatum-dependent habits are insensitive to both increases and decreases in reinforcer value in mice.

    Science.gov (United States)

    Quinn, Jennifer J; Pittenger, Christopher; Lee, Anni S; Pierson, Jamie L; Taylor, Jane R

    2013-03-01

    The mouse has emerged as an advantageous species for studying the brain circuitry that underlies complex behavior and for modeling neuropsychiatric disease. The transition from flexible, goal-directed actions to inflexible, habitual responses is argued to be a valid and reliable behavioral model for studying a core aspect of corticostriatal systems that is implicated in certain forms of psychopathology. This transition is thought to correspond to a progression of behavioral control from associative to sensorimotor corticobasal ganglia networks. Habits form following extensive training and are characterized by reduced sensitivity of instrumental responding to reinforcer revaluation; few studies have examined this form of behavioral control in mice. Here we examined the involvement of the dorsolateral and dorsomedial striatum in this transition in the C57BL/6 inbred mouse strain. We provided evidence that damage to the dorsolateral striatum disrupted habitual responding, i.e. it preserved sensitivity to changes in outcome value following either outcome devaluation or, shown for the first time in mice, outcome inflation. Together, these data show that instrumental responding in lesioned mice tracks the current value of a reinforcer and provide evidence that neuroanatomical mechanisms underlying habit learning in rats are preserved in the mouse. This will allow for the genetic and molecular dissection of neural factors involved in decision-making and mechanisms of aberrant habit formation. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. Use of 76Br-bromospiperone for the analysis of dopamine receptors in neuroleptic treated patients

    International Nuclear Information System (INIS)

    Maziere, B.; Cambon, H.; Baron, J.C.; Loc'h, C.

    1987-06-01

    The determination of the optimal prescription dosage of neuroleptic medications is of great importance to optimize the therapeutic response and to minimize the occurrence of tardive dyskinesia and other side-effects. PET, a non-invasive methodology which provides in-vivo the actual binding (occupation) of brain dopamine receptors, can be used as an in-vivo radioreceptor assay to indirectly estimate the neuroleptic tissue levels. In this study, 76Br-BSP was used in conjunction with PET to provide a semi-quantitative estimate of the neuroleptic (D2) binding sites occupancy rate during and following oral treatment by neuroleptics. On neuroleptic treatment, the fraction of unoccupied sites showed a striking dose-dependence ranging from .94 to .27 for lowest and highest doses. The CPZ equivalent daily oral doses occupying 50 and 100% of the neuroleptic sites were found to be respectively about 6 and 60 μmol/kg. The results establish that washout of neuroleptics from striatal binding sites is a rapid process that strongly suggest that the long-lasting remissions of psychotic patients following neuroleptic withdrawal are not due to persistent dopamine receptor occupation

  19. Attention modulates the dorsal striatum response to love stimuli.

    Science.gov (United States)

    Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

    2014-02-01

    In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

  20. Shape abnormalities of the striatum in Alzheimer's disease.

    Science.gov (United States)

    de Jong, Laura W; Ferrarini, Luca; van der Grond, Jeroen; Milles, Julien R; Reiber, Johan H C; Westendorp, Rudi G J; Bollen, Edward L E M; Middelkoop, Huub A M; van Buchem, Mark A

    2011-01-01

    Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected.

  1. Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

    Science.gov (United States)

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

    2011-01-01

    Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

  2. A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

    Science.gov (United States)

    McDonald, R J; Hong, N S

    2004-01-01

    This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

  3. Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

    Science.gov (United States)

    Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

    2018-02-28

    Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of

  4. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Directory of Open Access Journals (Sweden)

    Makoto Ito

    2015-11-01

    Full Text Available Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS, the dorsomedial striatum (DMS, and the ventral striatum (VS identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  5. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Science.gov (United States)

    Ito, Makoto; Doya, Kenji

    2015-11-01

    Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS), the dorsomedial striatum (DMS), and the ventral striatum (VS) identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  6. Amygdala and ventral striatum make distinct contributions to reinforcement learning

    Science.gov (United States)

    Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

    2016-01-01

    Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

  7. Spike-timing dependent plasticity in the striatum

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2010-06-01

    Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

  8. Neuronal basis for evaluating selected action in the primate striatum.

    Science.gov (United States)

    Yamada, Hiroshi; Inokawa, Hitoshi; Matsumoto, Naoyuki; Ueda, Yasumasa; Kimura, Minoru

    2011-08-01

    Humans and animals optimize their behavior by evaluating outcomes of individual actions and predicting how much reward the actions will yield. While the estimated values of actions guide choice behavior, the choices are also governed by other behavioral norms, such as rules and strategies. Values, rules and strategies are represented in neuronal activity, and the striatum is one of the best qualified brain loci where these signals meet. To understand the role of the striatum in value- and strategy-based decision-making, we recorded striatal neurons in macaque monkeys performing a behavioral task in which they searched for a reward target by trial-and-error among three alternatives, earned a reward for a target choice, and then earned additional rewards for choosing the same target. This task allowed us to examine whether and how values of targets and strategy, which were defined as negative-then-search and positive-then-repeat (or win-stay-lose-switch), are represented in the striatum. Large subsets of striatal neurons encoded positive and negative outcome feedbacks of individual decisions and actions. Once monkeys made a choice, signals related to chosen actions, their values and search- or repeat-type actions increased and persisted until the outcome feedback appeared. Subsets of neurons exhibited a tonic increase in activity after the search- and repeat-choices following negative and positive feedback in the last trials as the task strategy monkeys adapted. These activity profiles as a heterogeneous representation of decision variables may underlie a part of the process for reinforcement- and strategy-based evaluation of selected actions in the striatum. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  9. Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

    Directory of Open Access Journals (Sweden)

    Louise eAdermark

    2011-10-01

    Full Text Available The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABAA and glycine receptors in regulating synaptic activity in the dorsolateral (DLS and ventral striatum (nucleus accumbens, nAc. Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABAA receptors and strychnine-sensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 µM, inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM and blocked by GABAA receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially sub-region specific manner.

  10. Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli

    Directory of Open Access Journals (Sweden)

    Lanuza Enrique

    2007-11-01

    Full Text Available Abstract Background Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae. The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja. Results Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections. Conclusion The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse.

  11. Aversive counterconditioning attenuates reward signalling in the ventral striatum

    Directory of Open Access Journals (Sweden)

    Anne Marije Kaag

    2016-08-01

    Full Text Available Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient rewards such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional Magnetic Resonance Imaging (fMRI. In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signalling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signalling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

  12. The involvement of the striatum in decision making

    Science.gov (United States)

    Goulet-Kennedy, Julie; Labbe, Sara; Fecteau, Shirley

    2016-01-01

    Decision making has been extensively studied in the context of economics and from a group perspective, but still little is known on individual decision making. Here we discuss the different cognitive processes involved in decision making and its associated neural substrates. The putative conductors in decision making appear to be the prefrontal cortex and the striatum. Impaired decision-making skills in various clinical populations have been associated with activity in the prefrontal cortex and in the striatum. We highlight the importance of strengthening the degree of integration of both cognitive and neural substrates in order to further our understanding of decision-making skills. In terms of cognitive paradigms, there is a need to improve the ecological value of experimental tasks that assess decision making in various contexts and with rewards; this would help translate laboratory learnings into real-life benefits. In terms of neural substrates, the use of neuroimaging techniques helps characterize the neural networks associated with decision making; more recently, ways to modulate brain activity, such as in the prefrontal cortex and connected regions (eg, striatum), with noninvasive brain stimulation have also shed light on the neural and cognitive substrates of decision making. Together, these cognitive and neural approaches might be useful for patients with impaired decision-making skills. The drive behind this line of work is that decision-making abilities underlie important aspects of wellness, health, security, and financial and social choices in our daily lives. PMID:27069380

  13. Regional specialization within the human striatum for diverse psychological functions.

    Science.gov (United States)

    Pauli, Wolfgang M; O'Reilly, Randall C; Yarkoni, Tal; Wager, Tor D

    2016-02-16

    Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone.

  14. 1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity.

    Science.gov (United States)

    Lorenc-Koci, Elzbieta; Gołembiowska, Krystyna; Wardas, Jadwiga

    2005-07-27

    Malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, is frequently used as a model neurotoxin to produce lesion of the nigrostriatal dopaminergic system in animals due to particular sensitivity of dopamine neurons to mild energy impairment. This model of neurotoxicity was applied in our study to explore neuroprotective potential of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance whose function in the mammalian brain, despite extensive studies, has not been elucidated so far. Injection of malonate at a dose of 3 mumol unilaterally into the rat left medial forebrain bundle resulted in the 54% decrease in dopamine (DA) concentration in the ipsilateral striatum and, depending on the examined striatum regions, caused 24-44% reduction in [3H]GBR12,935 binding to the dopamine transporter (DAT). TIQ (50 mg/kg i.p.) administered 4 h before malonate infusion and next once daily for successive 7 days prevented both these effects of malonate. Such TIQ treatment restored DA content and DAT binding almost to the control level. The results of the present study indicate that TIQ may act as a neuroprotective agent in the rat brain. An inhibition of the enzymatic activities of monoamine oxidase and gamma-glutamyl transpeptidase as well as an increase in the striatal levels of glutathione and nitric oxide found after TIQ administration and reported in our earlier studies are considered to be potential factors that may be involved in the TIQ-mediated protection of dopamine terminals from malonate toxicity.

  15. Comparative study of D2 receptors and content of DA in striatum before and after electro-acupuncture treatment

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    1999-01-01

    Objective: To evaluate the change of D 2 receptors and its relationship with DA content in experimental hemi-parkinsonism rats before and after electron-acupuncture treatment. Methods: 125 I-IBZM D 2 receptor cerebral autoradiographic analysis, HPLC-ECD DA and its metabolites, homovanillic acid (HVA), 3,4-di-hydroxyphenylacetic acid (DOPAC) content detection were used to study in striatum in before treatment, electro-acupuncture treatment and treatment control group. Results: 1) The DA, HVA and DOPAC level in striatum of lesioned side in electro-acupuncture group was increased comparing with the before treatment and treatment control group (P 125 I-IBZM uptake ratio was 8.04 +- 0.71, (29.34 +- 4.83)% more than that of the contralateral side, but no significant difference was observed as compared with that of the pretreatment group [(8.09 +- 0.52), P>0.05]; however it was much lower than that of the treatment control group (8.61 +- 0.63), P 2 receptors' up regulation in rats with experimental hemi-parkinsonism

  16. A functional difference in information processing between orbitofrontal cortex and ventral striatum during decision-making behaviour.

    Science.gov (United States)

    Stott, Jeffrey J; Redish, A David

    2014-11-05

    Both orbitofrontal cortex (OFC) and ventral striatum (vStr) have been identified as key structures that represent information about value in decision-making tasks. However, the dynamics of how this information is processed are not yet understood. We recorded ensembles of cells from OFC and vStr in rats engaged in the spatial adjusting delay-discounting task, a decision-making task that involves a trade-off between delay to and magnitude of reward. Ventral striatal neural activity signalled information about reward before the rat's decision, whereas such reward-related signals were absent in OFC until after the animal had committed to its decision. These data support models in which vStr is directly involved in action selection, but OFC processes decision-related information afterwards that can be used to compare the predicted and actual consequences of behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  17. Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lypopolysaccharide in the hippocampus and striatum of male mice

    Energy Technology Data Exchange (ETDEWEB)

    Astiz, Mariana, E-mail: marianaastiz@gmail.com; Diz-Chaves, Yolanda, E-mail: ydiz@cajal.csic.es; Garcia-Segura, Luis M., E-mail: lmgs@cajal.csic.es

    2013-10-15

    Dimethoate is an organophosphorus insecticide extensively used in horticulture. Previous studies have shown that the administration of dimethoate to male rats, at a very low dose and during a sub-chronic period, increases the oxidation of lipids and proteins, reduces the levels of antioxidants and impairs mitochondrial function in various brain regions. In this study, we have assessed in C57Bl/6 adult male mice, whether sub-chronic (5 weeks) intoxication with a low dose of dimethoate (1.4 mg/kg) affects the expression of inflammatory molecules and the reactivity of microglia in the hippocampus and striatum under basal conditions and after an immune challenge caused by the systemic administration of lipopolysaccharide. Dimethoate increased mRNA levels of tumor necrosis factor α (TNFα) and interleukin (IL) 6 in the hippocampus, and increased the proportion of Iba1 immunoreactive cells with reactive phenotype in dentate gyrus and striatum. Lipopolysaccharide caused a significant increase in the mRNA levels of IL1β, TNFα, IL6 and interferon-γ-inducible protein 10, and a significant increase in the proportion of microglia with reactive phenotype in the hippocampus and the striatum. Some of the effects of lipopolysaccharide (proportion of Iba1 immunoreactive cells with reactive phenotype and IL6 mRNA levels) were amplified in the animals treated with dimethoate, but only in the striatum. These findings indicate that a sub-chronic period of administration of a low dose of dimethoate, comparable to the levels of the pesticide present as residues in food, causes a proinflammatory status in the brain and enhances the neuroinflammatory response to the lipopolysaccharide challenge with regional specificity. - Highlights: • The dose of pesticide used was comparable to the levels of residues found in food. • Dimethoate administration increased cytokine expression and microglia reactivity. • Hippocampus and striatum were differentially affected by the treatment.

  18. Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

    Science.gov (United States)

    Goodman, J; Leong, K-C; Packard, M G

    2015-12-17

    Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

  19. Enhancing and impairing extinction of habit memory through modulation of NMDA receptors in the dorsolateral striatum.

    Science.gov (United States)

    Goodman, Jarid; Ressler, Reed L; Packard, Mark G

    2017-06-03

    The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder). Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. The role of the intrinsic cholinergic system of the striatum: What have we learned from TAN recordings in behaving animals?

    Science.gov (United States)

    Apicella, Paul

    2017-09-30

    Cholinergic interneurons provide rich local innervation of the striatum and play an important role in controlling behavior, as evidenced by the variety of movement and psychiatric disorders linked to disrupted striatal cholinergic transmission. Much progress has been made in recent years regarding our understanding of how these interneurons contribute to the processing of information in the striatum. In particular, investigation of the activity of presumed striatal cholinergic interneurons, identified as tonically active neurons or TANs in behaving animals, has pointed to their role in the signaling and learning of the motivational relevance of environmental stimuli. Although the bulk of this work has been conducted in monkeys, several studies have also been carried out in behaving rats, but information remains rather disparate across studies and it is still questionable whether rodent TANs correspond to TANs described in monkeys. Consequently, our current understanding of the function of cholinergic transmission in the striatum is challenged by the rapidly growing, but often confusing literature on the relationship between TAN activity and specific behaviors. As regards the precise nature of the information conveyed by the cholinergic TANs, a recent influential view emphasized that these local circuit neurons may play a special role in the processing of contextual information that is important for reinforcement learning and selection of appropriate actions. This review provides a summary of recent progress in TAN physiology from which it is proposed that striatal cholinergic interneurons are crucial elements for flexible switching of behaviors under changing environmental conditions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    International Nuclear Information System (INIS)

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-01-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states

  2. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  3. 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

  4. Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

    International Nuclear Information System (INIS)

    Goeders, N.E.; Kuhar, M.J.

    1987-01-01

    A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of [ 3 H]sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems

  5. Cocaine exposure shifts the balance of associative encoding from ventral to dorsolateral striatum

    Directory of Open Access Journals (Sweden)

    Yuji Takahashi

    2007-12-01

    Full Text Available Both dorsal and ventral striatum are implicated in the "habitization" of behavior that occurs in addiction. Here we examined the effect of cocaine exposure on associative encoding in these two regions. Neural activity was recorded during go/no-go discrimination learning and reversal. Activity in ventral striatum developed and reversed rapidly, tracking the valence of the predicted outcome, whereas activity in dorsolateral striatum developed and reversed more slowly, tracking discriminative responding. This difference is consistent with the putative roles of these two areas in promoting habit-like behavior. Dorsolateral striatum has been directly implicated in habit or stimulus response learning, whereas ventral striatum appears to be involved indirectly by allowing cues associated with reward to exert a general motivational influence on responding. Interestingly cocaine exposure did not uniformly enhance processing across both regions. Instead cocaine reduced the degree and flexibility of cue-evoked firing in ventral striatum while marginally enhanced cue-selective firing in dorsolateral striatum. Thus cocaine exposure causes regionally specific effects on neural processing in striatum; these effects may promote the habitization of behavior by shifting control from ventral to dorsolateral regions.

  6. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  7. Molecular and functional definition of the developing human striatum.

    Science.gov (United States)

    Onorati, Marco; Castiglioni, Valentina; Biasci, Daniele; Cesana, Elisabetta; Menon, Ramesh; Vuono, Romina; Talpo, Francesca; Laguna Goya, Rocio; Lyons, Paul A; Bulfamante, Gaetano P; Muzio, Luca; Martino, Gianvito; Toselli, Mauro; Farina, Cinthia; Barker, Roger A; Biella, Gerardo; Cattaneo, Elena

    2014-12-01

    The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal genes, including those encoding transcription factors, that distinguished striatal from neocortical identities. Unexpected differences from mouse striatal development were discovered. We monitored 36 determinants at the protein level, revealing regional domains of expression and their refinement, during striatal development. We electrophysiologically profiled human striatal neurons differentiated in vitro and determined their refined molecular and functional properties. These results provide a resource and opportunity to gain global understanding of how transcriptional and functional processes converge to specify human striatal and neocortical neurons during development.

  8. Paralimbic system and striatum are involved in motivational behavior.

    Science.gov (United States)

    Nishimura, Masahiko; Yoshii, Yoshihiko; Watanabe, Jobu; Ishiuchi, Shogo

    2009-10-28

    Goal-directed rewarded behavior and goal-directed non-rewarded behavior are concerned with motivation. However, the neural substrates involved in goal-directed non-rewarded behaviors are unknown. Using functional magnetic resonance imaging, we investigated the brain activities of healthy individuals during a novel tool use (turning a screwdriver) to elucidate the relationship between the brain mechanism relevant to goal-directed non-rewarded behavior and motivation. We found that our designed behavioral task evoked activities in the orbitofrontal cortex, striatum, anterior insula, lateral prefrontal cortex, and anterior cingulate cortex compared with a meaningless task. These results suggest that activation in these cerebral regions play important roles in motivational behavior without tangible rewards.

  9. Enhancement of striatum-dependent memory by conditioned fear is mediated by beta-adrenergic receptors in the basolateral amygdala

    Directory of Open Access Journals (Sweden)

    Travis D. Goode

    2016-06-01

    Full Text Available Emotional arousal can have a profound impact on various learning and memory processes. For example, unconditioned emotional stimuli (e.g., predator odor or anxiogenic drugs enhance dorsolateral striatum (DLS-dependent habit memory. These effects critically depend on a modulatory role of the basolateral complex of the amygdala (BLA. Recent work indicates that, like unconditioned emotional stimuli, exposure to an aversive conditioned stimulus (CS (i.e., a tone previously paired with shock can also enhance consolidation of DLS-dependent habit memory. The present experiments examined whether noradrenergic activity, particularly within the BLA, is required for a fear CS to enhance habit memory consolidation. First, rats underwent a fear conditioning procedure in which a tone CS was paired with an aversive unconditioned stimulus. Over the course of the next five days, rats received training in a DLS-dependent water plus-maze task, in which rats were reinforced to make a consistent body-turn response to reach a hidden escape platform. Immediately after training on days 1–3, rats received post-training systemic (Experiment 1 or intra-BLA (Experiment 2 administration of the β-adrenoreceptor antagonist, propranolol. Immediately after drug administration, half of the rats were re-exposed to the tone CS in the conditioning context (without shock. Post-training CS exposure enhanced consolidation of habit memory in vehicle-treated rats, and this effect was blocked by peripheral (Experiment 1 or intra-BLA (Experiment 2 propranolol administration. The present findings reveal that noradrenergic activity within the BLA is critical for the enhancement of DLS-dependent habit memory as a result of exposure to conditioned emotional stimuli.

  10. Art for reward's sake: visual art recruits the ventral striatum.

    Science.gov (United States)

    Lacey, Simon; Hagtvedt, Henrik; Patrick, Vanessa M; Anderson, Amy; Stilla, Randall; Deshpande, Gopikrishna; Hu, Xiaoping; Sato, João R; Reddy, Srinivas; Sathian, K

    2011-03-01

    A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non-art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Inhibiting PKM[zeta] Reveals Dorsal Lateral and Dorsal Medial Striatum Store the Different Memories Needed to Support Adaptive Behavior

    Science.gov (United States)

    Pauli, Wolfgang M.; Clark, Alexandra D.; Guenther, Heidi J.; O'Reilly, Randall C.; Rudy, Jerry W.

    2012-01-01

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or…

  12. Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

    Science.gov (United States)

    Contreras-Rodríguez, Oren; Martín-Pérez, Cristina; Vilar-López, Raquel; Verdejo-Garcia, Antonio

    2017-05-01

    The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Dorsolateral Striatum Engagement Interferes with Early Discrimination Learning

    Directory of Open Access Journals (Sweden)

    Hadley C. Bergstrom

    2018-05-01

    Full Text Available Summary: In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning. : What is the contribution of the DLS in early discrimination learning? Bergstrom et al. show using in vivo optogenetics, fluorescence in situ hybridization, and brain-wide activity mapping that silencing the DLS facilitates early discrimination learning, drives activity in a parallel PL-DMS circuit, and preferentially recruits the DLS “direct” output pathway. Keywords: striatum, reward, goal-directed, habit, optogenetics, plasticity, cognition, Arc

  14. Contingency learning in human fear conditioning involves the ventral striatum.

    Science.gov (United States)

    Klucken, Tim; Tabbert, Katharina; Schweckendiek, Jan; Merz, Christian Josef; Kagerer, Sabine; Vaitl, Dieter; Stark, Rudolf

    2009-11-01

    The ability to detect and learn contingencies between fearful stimuli and their predictive cues is an important capacity to cope with the environment. Contingency awareness refers to the ability to verbalize the relationships between conditioned and unconditioned stimuli. Although there is a heated debate about the influence of contingency awareness on conditioned fear responses, neural correlates behind the formation process of contingency awareness have gained only little attention in human fear conditioning. Recent animal studies indicate that the ventral striatum (VS) could be involved in this process, but in human studies the VS is mostly associated with positive emotions. To examine this question, we reanalyzed four recently published classical fear conditioning studies (n = 117) with respect to the VS at three distinct levels of contingency awareness: subjects, who did not learn the contingencies (unaware), subjects, who learned the contingencies during the experiment (learned aware) and subjects, who were informed about the contingencies in advance (instructed aware). The results showed significantly increased activations in the left and right VS in learned aware compared to unaware subjects. Interestingly, this activation pattern was only found in learned but not in instructed aware subjects. We assume that the VS is not involved when contingency awareness does not develop during conditioning or when contingency awareness is unambiguously induced already prior to conditioning. VS involvement seems to be important for the transition from a contingency unaware to a contingency aware state. Implications for fear conditioning models as well as for the contingency awareness debate are discussed.

  15. The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

    Directory of Open Access Journals (Sweden)

    Todd M. Mowery

    2017-06-01

    Full Text Available Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL, are commonly linked with processing deficits at or below the level of the auditory cortex (ACx. However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.

  16. Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

    Science.gov (United States)

    Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

    2012-01-01

    The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

  17. Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

    Science.gov (United States)

    Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan

    2016-04-01

    One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Prior Cocaine Self-Administration Increases Response-Outcome Encoding That Is Divorced from Actions Selected in Dorsal Lateral Striatum.

    Science.gov (United States)

    Burton, Amanda C; Bissonette, Gregory B; Zhao, Adam C; Patel, Pooja K; Roesch, Matthew R

    2017-08-09

    Dorsal lateral striatum (DLS) is a highly associative structure that encodes relationships among environmental stimuli, behavioral responses, and predicted outcomes. DLS is known to be disrupted after chronic drug abuse; however, it remains unclear what neural signals in DLS are altered. Current theory suggests that drug use enhances stimulus-response processing at the expense of response-outcome encoding, but this has mostly been tested in simple behavioral tasks. Here, we investigated what neural correlates in DLS are affected by previous cocaine exposure as rats performed a complex reward-guided decision-making task in which predicted reward value was independently manipulated by changing the delay to or size of reward associated with a response direction across a series of trial blocks. After cocaine self-administration, rats exhibited stronger biases toward higher-value reward and firing in DLS more strongly represented action-outcome contingencies independent from actions subsequently taken rather than outcomes predicted by selected actions (chosen-outcome contingencies) and associations between stimuli and actions (stimulus-response contingencies). These results suggest that cocaine self-administration strengthens action-outcome encoding in rats (as opposed to chosen-outcome or stimulus-response encoding), which abnormally biases behavior toward valued reward when there is a choice between two options during reward-guided decision-making. SIGNIFICANCE STATEMENT Current theories suggest that the impaired decision-making observed in individuals who chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome (R-O) and stimulus-response associations, respectively. We examined the impact that prior cocaine self-administration had on firing in dorsal lateral striatum (DLS), a brain area known to be involved in habit formation and affected by drugs of abuse

  19. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

    Science.gov (United States)

    Sagredo, Onintza; González, Sara; Aroyo, Ilia; Pazos, María Ruth; Benito, Cristina; Lastres-Becker, Isabel; Romero, Juan P.; Tolón, Rosa M.; Mechoulam, Raphael; Brouillet, Emmanuel; Romero, Julián; Fernández-Ruiz, Javier

    2009-01-01

    Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington’s disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be up-regulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. PMID:19115380

  20. Decrease in the number of rat brain dopamine and muscarinic receptors after chronic alcohol intake

    International Nuclear Information System (INIS)

    Syvaelahti, E.K.G.; Hietala, J.; Roeyttae, M.; Groenroos, J.

    1988-01-01

    The effect of 32 weeks' alcohol treatment on the number and affinity of dopamine and muscarinic receptor sites in rat striatum were measured using 3 H-spiperone and 3 H-quinuclidinylbenzilate ( 3 H-QNB) as radioligans. The number of dopamine receptor sites was 38 per cent and the number of muscarinic receptor sites 36 per cent lower in the alcohol group than in control rats. The differences in receptor affinities were less marked. In conclusion, a long-term alcohol intake with rather moderate doses seems to induce a pronounced down-regulation in dopamine and muscarinic receptor systems in rat striatum. (author)

  1. Neuroimaging studies of the striatum in cognition Part I: healthy individuals.

    Science.gov (United States)

    Provost, Jean-Sebastien; Hanganu, Alexandru; Monchi, Oury

    2015-01-01

    The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.

  2. BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

    Science.gov (United States)

    Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

    2016-09-01

    According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

  3. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

    Science.gov (United States)

    Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko

    2015-01-01

    Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384

  4. Time-dependent effects of repeated THC treatment on dopamine D2/3 receptor-mediated signalling in midbrain and striatum.

    Science.gov (United States)

    Tournier, Benjamin B; Tsartsalis, Stergios; Dimiziani, Andrea; Millet, Philippe; Ginovart, Nathalie

    2016-09-15

    This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D2/3R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D2/3R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D2/3R function and a decreased DA presynaptic signaling, mediated by increased D2/3R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D2/3R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

    Science.gov (United States)

    Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

    2016-01-20

    Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

  6. Hemiballism due to the lesion in the striatum demonstrated by CT scan

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, S; Ito, N; Hirayama, K [Chiba Univ. (Japan). School of Medicine; Tochigi, S

    1981-09-01

    Two cases of hemiballism due to vascular lesions in the striatum demonstrated by CT scan were reported. Case 1 was a 58-year-old man with hypertension and diabetes mellitus, who had cerebral hemorrhage in the right striatum. Hemiballistic movements, which were confined to his face, neck and trunk as well as limbs of the left side, appeared soon after CVA and improved on treatment with haloperidol up to 4 mg per day. Case 2 was a 63-year-old woman with hypertension, who had probable cerebral infarct in the right striatum. The hemiballistic movements, confined to her right side, appeared soon after CVA and improved on treatment with chlorpromazine up to 50 mg per day, and perphenazine up to 6 mg per day. Whereas case 1 had contralateral hemiballism, case 2 had homolateral hemiballism, both due to vascular lesions in the striatum. Although it has been generally accepted, from postmortem and experimental studies, that the lesion responsible for hemiballism was localized in the contralateral subthalamic nucleus, a few cases of hemiballism have been reported, in which the subthalamic nucleus (Luys' body) and its connections appeared to be intact at necropsy. The present cases of hemiballism with involvement of the striatum without involvement of the subthalamic nucleus by CT scan, seem to be the first reported cases. It is not clear in the CT scan whether the subthalamic nucleus is also involved in addition to the striatal lesion, however, it is unlikely due to different vascular supplies to these areas. From a clinical and an experimental point of view, we would like to propose that hemiballism can occur due to the lesion in the striatum, especially the caudate nucleus even when the subthalamic nucleus and its connections are intact.

  7. Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

    Science.gov (United States)

    Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

    2011-05-01

    Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Functional responses of pre- and postsynaptic dopamine D2 receptors in rat brain striatum

    OpenAIRE

    Ma, Guofen

    2014-01-01

    El sistema dopaminèrgic has estat molt estudiat en els darrers anys, principalment degut a la seva implicació en diverses patologies com la malaltia de Parkinson, la esquizofrènia o la síndrome de Tourette, així com també en l'abús de drogues. S'han descrit cinc subtipus de receptors per la dopamina (DA), tots els quals pertanyen a la família de receptors acoblats a proteïnes G (GPCRs). D'aquests cinc subtipus, els receptors D2 son la diana principal dels antipsicòtics (antagonistes) i també ...

  9. Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

    Science.gov (United States)

    Pierozan, Paula; Biasibetti-Brendler, Helena; Schmitz, Felipe; Ferreira, Fernanda; Pessoa-Pureur, Regina; Wyse, Angela T S

    2018-06-01

    Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity.

  10. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  11. Hints on the Lateralization of Dopamine Binding to D-1 Receptors in Rat Striatum

    Czech Academy of Sciences Publication Activity Database

    Franco, R.; Casadó-Anguera, V.; Muňoz, A.; Petrovič, Miloš; Navarro, G.; Moreno, E.; Lanciego, J. L.; Labandeira-García, J. L.; Cortés, A.; Casadó, V.

    2016-01-01

    Roč. 53, č. 8 (2016), s. 5436-5445 ISSN 0893-7648 Institutional support: RVO:67985823 Keywords : lateralization * basal ganglia * G-protein-coupled receptor dimer * dyskinesia * 6-hydroxydopamine Subject RIV: ED - Physiology Impact factor: 6.190, year: 2016

  12. Quinolinic acid induced neurodegeneration in the striatum: a combined in vivo and in vitro analysis of receptor changes and microglia activation

    International Nuclear Information System (INIS)

    Moresco, R.M.; Lavazza, T.; Belloli, S.; Todde, S.; Matarrese, M.; Carpinelli, A.; Turolla, E.; Fazio, F.; Lecchi, M.; Pezzola, A.; Popoli, P.; Zimarino, V.; Malgaroli, A.

    2008-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this human neurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A 2A and dopamine D 2 receptors) together with the degree of microglia activation. Both approaches showed a loss of adenosine A 2A and dopamine D 2 receptors paralleled by an increase of microglial activation. This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to human patients. (orig.)

  13. Differences between Dorsal and Ventral Striatum in the Sensitivity of Tonically Active Neurons to Rewarding Events

    Directory of Open Access Journals (Sweden)

    Kevin Marche

    2017-07-01

    Full Text Available Within the striatum, cholinergic interneurons, electrophysiologically identified as tonically active neurons (TANs, represent a relatively homogeneous group in terms of their functional properties. They display typical pause in tonic firing in response to rewarding events which are of crucial importance for reinforcement learning. These responses are uniformly distributed throughout the dorsal striatum (i.e., motor and associative striatum, but it is unknown, at least in monkeys, whether differences in the modulation of TAN activity exist in the ventral striatum (i.e., limbic striatum, a region specialized for processing of motivational information. To address this issue, we examined the activity of dorsal and ventral TANs in two monkeys trained on a Pavlovian conditioning task in which a visual stimulus preceded the delivery of liquid reward by a fixed time interval. We found that the proportion of TANs responding to the stimulus predictive of reward did not vary significantly across regions (58%–80%, whereas the fraction of TANs responding to reward was higher in the limbic striatum (100% compared to the motor (65% and associative striatum (52%. By examining TAN modulation at the level of both the population and the individual neurons, we showed that the duration of pause responses to the stimulus and reward was longer in the ventral than in the dorsal striatal regions. Also, the magnitude of the pause was greater in ventral than dorsal striatum for the stimulus predictive of reward but not for the reward itself. We found similar region-specific differences in pause response duration to the stimulus when the timing of reward was less predictable (fixed replaced by variable time interval. Regional variations in the duration and magnitude of the pause response were transferred from the stimulus to reward when reward was delivered in the absence of any predictive stimulus. It therefore appears that ventral TANs exhibit stronger responses to

  14. Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.

    Directory of Open Access Journals (Sweden)

    Evgeny Bychkov

    Full Text Available G protein-coupled receptor kinases (GRKs and arrestins mediate desensitization of G protein-coupled receptors (GPCR. Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

  15. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

    NARCIS (Netherlands)

    Holz, N.E.; Boecker-Schlier, R.; Buchmann, A.F.; Blomeyer, D.; Jennen-Steinmetz, C.; Baumeister, S.; Plichta, M.M.; Cattrell, A.; Schumann, G.; Esser, G.; Schmidt, M.; Buitelaar, J.K.; Meyer-Lindenberg, A.; Banaschewski, T.; Brandeis, D.; Laucht, M.

    2017-01-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At

  16. Materials as regard about ecology and spreading of lycodine striatum bicolor nik in Tajikistan

    International Nuclear Information System (INIS)

    Sattorov, T.S.; Khidirov, Kh.; Mukhammadkulov, M.

    2003-01-01

    In this article is placed new scientific information about biology, ecology and spreading of Lycodine striatum bicolor within the territory of Tajikistan. Finding available in this article concerning spreading of flus snake are considered to be new. This scarce snake was discovered for the first time in Northern part of Tajikistan. This new information will enrich our notions about Reptile fauna of Tajikistan

  17. Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

    Science.gov (United States)

    Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

    2018-07-01

    The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

  18. Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

    Directory of Open Access Journals (Sweden)

    Kevin D. Alloway

    2017-07-01

    Full Text Available The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD and related neurological disorders.

  19. Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior

    NARCIS (Netherlands)

    van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.

    2014-01-01

    Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and

  20. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernández, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  1. Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernandez, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  2. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, Susanne; Klumpers, Floris; Schroeder, Tobias Navarro; Oplaat, Krista T.; Krugers, Harm J.; Oitzl, Melly S.; Joels, Marian; Doeller, Christian F.; Fernandez, Guillen

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  3. Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

    Science.gov (United States)

    Alloway, Kevin D.; Smith, Jared B.; Mowery, Todd M.; Watson, Glenn D. R.

    2017-01-01

    The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD) and related neurological disorders. PMID:28790899

  4. Comparative studies of D2 receptors and brain perfusion in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    The relationship between dopamine D 2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra (SN) and ventral tegmental area (VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125 I-IBZM ex-vivo autoradiography analysis and 99m Tc-HM-PAO regional cerebral biodistribution were used to evaluate D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 0.05). These results indicated that in the 6-OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D 2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  5. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  6. The role of the dorsoanterior striatum in implicit motivation: The case of the need for power

    Directory of Open Access Journals (Sweden)

    Oliver C Schultheiss

    2013-04-01

    Full Text Available Implicit motives like the need for power (nPower scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions in behavioral studies and (b activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2, 217-222 model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.

  7. Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

    Science.gov (United States)

    Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

    2016-12-14

    Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

  8. Serotonin 2A and 2C receptor biosynthesis in the rodent striatum during postnatal development: mRNA expression and functional linkage to neuropeptide gene regulation.

    Science.gov (United States)

    Basura, G J; Walker, P D

    2000-11-01

    The present study was designed to determine if there are region-specific differences in serotonin (5-HT) neurotransmission and 5-HT receptor expression that may limit the stimulatory effects of the 5-HT releaser p-chloroamphetamine (pCA) on striatal neuropeptide gene expression to the posterior striatum (P-STR) during postnatal maturation. Sprague-Dawley rat brains from postnatal days (PND) 1-35 were processed for 5-HT(2A) and 5-HT(2C) receptor mRNA expression by in situ hybridization and monoamine analysis by HPLC. Within the P-STR, 5-HT(2A) receptor mRNA expression reached young adult (PND 35) levels by PND 3, while levels in the A-STR were significantly less (range: 1.43 +/- 0.219-6. 36 +/- 0.478) than P-STR (5.36 +/- 0.854-12.11 +/- 1.08) at each respective age throughout the time course. 5-HT(2C) receptor mRNA expression reached young adult levels at PND 7 in the A-STR and by PND 3 in the P-STR. At each PND age 5-HT(2C) receptor mRNA levels within the P-STR were significantly less (6.23 +/- 1.02-12.32 +/- 0.427) than the A-STR (7.31 +/- 1.65-26.84 +/- 2.24). 5-HT content increased across the developmental time course within the P-STR (5.01 +/- 0.327-15.7 +/- 1.03 ng/mg protein) and A-STR (2.97 +/- 0. 223-11.2 +/- 0.701 ng/mg protein). Four hours following injection (i. p.) of pCA (10 mg/kg), preprotachykinin (PPT) mRNA levels increased 89% in the P-STR but not the anterior (A-STR) striatum of the 3-week-old rat, which were prevented by preinjection (30 min, i.p.) of the 5-HT(2) receptor antagonist ritanserin (1 mg/kg). Together, these data suggest that faster maturity of 5-HT(2A) receptor expression in the P-STR may be sufficient to convey the region-specific acute stimulatory effects of pCA on PPT mRNA transcription in the developing rodent striatum. These results provide further evidence that the influence of 5-HT on neuropeptide gene expression is far stronger in caudal vs. rostral striatal regions during postnatal development. Copyright 2000 Wiley

  9. Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

    Directory of Open Access Journals (Sweden)

    Miriam Matamales

    Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

  10. METHAMPHETAMINE-INDUCED CELL DEATH: SELECTIVE VULNERABILITY IN NEURONAL SUBPOPULATIONS OF THE STRIATUM IN MICE

    Science.gov (United States)

    ZHU, J. P. Q.; XU, W.; ANGULO, J. A.

    2010-01-01

    Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an indirect dopamine agonist. In the striatum, METH has been shown to cause long lasting neurotoxic damage to dopaminergic nerve terminals and recently, the degeneration and death of striatal cells. The present study was undertaken to identify the type of striatal neurons that undergo apoptosis after METH. Male mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h later. To demonstrate that METH induces apoptosis in neurons, we combined terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining with immunohistofluorescence for the neuronal marker neuron-specific nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout the striatum. METH induces apoptosis in approximately 25% of striatal neurons. Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, dorsolateral and ventrolateral quadrants of the striatum did not reveal anatomical preference. The type of striatal neuron undergoing cell death was determined by combining TUNEL with immunohistofluorescence for selective markers of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45% of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of cholinergic neurons in the dorsal–medial striatum. In contrast, the SST-positive interneurons were refractory to METH-induced apoptosis. Finally, the amount of cell loss determined with Nissl staining correlated with the amount of TUNEL staining in the striatum of METH-treated animals. In conclusion, some of the striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH. This

  11. The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum's Olfactory Tubercle

    Science.gov (United States)

    Gadziola, Marie A.

    2016-01-01

    The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we

  12. Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

    International Nuclear Information System (INIS)

    Ceballos, M.L. de; Boyce, S.; Taylor, M.; Jenner, P.; Marsden, C.D.

    1987-01-01

    Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens

  13. Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

    Energy Technology Data Exchange (ETDEWEB)

    Ceballos, M.L. de; Boyce, S; Taylor, M; Jenner, P; Marsden, C D

    1987-03-20

    Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens.

  14. Synergistic Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Angiogenesis Markers of Parkinsonian Rats

    Directory of Open Access Journals (Sweden)

    Seyed Abdollah Hashemvarzi

    2016-03-01

    Full Text Available Abstract: Parkinson is a progressive neurodegenerative disease in central nervous system. Non-pharmacologic treatment methods such as stem cell transplantation and exercise have been considered as a treatment. The purpose of this study was to evaluate the synergistic effects of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. 42 rats were divided into six groups: Normal (N, Sham (S, Parkinson’s (P, Stem cells transplanted Parkinson’s (SP, Exercised Parkinson’s (EP and Stem cells transplanted+Exercised Parkinson’s (SEP. To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats aged 6-8 weeks. After cultivation, approximately 5×105 cells were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on treadmill with a speed of 15 meters per minute. At the end of the study, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF, dopamine (DA and tyrosine hydroxylase (TH levels. VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP, especially in SEP group compared to P group after treatment (P<0.05. The BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats. Keywords: Stem cells, Aerobic exercise, Neurotrophic factors, Parkinson

  15. Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

    Science.gov (United States)

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

    2014-01-01

    Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

  16. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

    Directory of Open Access Journals (Sweden)

    Silvana Vargas Superti

    2009-04-01

    Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

  17. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval.

    Science.gov (United States)

    Vanelzakker, Michael B; Zoladz, Phillip R; Thompson, Vanessa M; Park, Collin R; Halonen, Joshua D; Spencer, Robert L; Diamond, David M

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  18. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala and Striatum Following Long-Term Spatial Memory Retrieval

    Directory of Open Access Journals (Sweden)

    Michael B VanElzakker

    2011-06-01

    Full Text Available We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 hr later. Rat brains were extracted 30 min after the 24 hr memory test trial for analysis of c-fos mRNA. Four groups were tested: 1 Rats given standard training (Standard; 2 Rats given cat exposure (Predator Stress 30 min prior to training (Pre-Training Stress; 3 Rats given water exposure only (Water Yoked; and 4 Rats given no water exposure (Home Cage. The Standard trained group exhibited excellent 24 hr memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA. The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  19. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

    Science.gov (United States)

    VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

  20. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

  1. Ventral striatum activation to prosocial rewards predicts longitudinal declines in adolescent risk taking.

    Science.gov (United States)

    Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Galván, Adriana

    2013-01-01

    Adolescence is a period of intensified emotions and an increase in motivated behaviors and passions. Evidence from developmental neuroscience suggests that this heightened emotionality occurs, in part, due to a peak in functional reactivity to rewarding stimuli, which renders adolescents more oriented toward reward-seeking behaviors. Most prior work has focused on how reward sensitivity may create vulnerabilities, leading to increases in risk taking. Here, we test whether heightened reward sensitivity may potentially be an asset for adolescents when engaged in prosocial activities. Thirty-two adolescents were followed over a one-year period to examine whether ventral striatum activation to prosocial rewards predicts decreases in risk taking over a year. Results show that heightened ventral striatum activation to prosocial stimuli relates to longitudinal declines in risk taking. Therefore, the very same neural region that has conferred vulnerability for adolescent risk taking may also be protective against risk taking. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

    Science.gov (United States)

    Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting

    2016-10-05

    An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

  3. SELEKSI RUMPUT LAUT Kappaphycus striatum DALAM UPAYA PENINGKATAN LAJU PERTUMBUHAN BIBIT UNTUK BUDIDAYA

    Directory of Open Access Journals (Sweden)

    Andi Parenrengi

    2017-01-01

    Full Text Available Budidaya rumput laut di Indonesia semakin berkembang seiring dengan peningkatan permintaan bahan baku industri untuk pasar domestik dan eksport. Rumput laut Kappaphycus striatum, salah satu spesies rumput laut komersil, telah intensif dibudidayakan di perairan pantai. Saat ini, masalah utama yang dihadapi pembudidaya adalah rendahnya kualitas bibit yang berasal dari hasil budidaya. Seleksi varietas merupakan salah satu metode yang diharapkan dapat meningkatkan laju pertumbuhan rumput laut. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh seleksi varietas terhadap pertumbuhan rumput laut sehingga dapat dilakukan produksi bibit unggul untuk keperluan budidaya. Budidaya rumput laut K. striatum telah dilakukan di Teluk Laikang, Kabupaten Takalar, Provinsi Sulawesi Selatan dengan menggunakan metode long line. Seleksi varietas dilakukan berdasarkan parameter laju pertumbuhan harian (LPH dan metode seleksi mengacu pada protokol seleksi yang telah dikembangkan pada rumput laut K. alvarezii. Hasil penelitian menunjukkan bahwa LPH bibit hasil seleksi lebih tinggi (P

  4. Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2004-01-01

    Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2→3.9%, CA: 57.4→14.1%, ST: 17.7→0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction

  5. Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2{yields}3.9%, CA: 57.4{yields}14.1%, ST: 17.7{yields}0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction.

  6. Existence and control of Go/No-Go decision transition threshold in the striatum.

    Directory of Open Access Journals (Sweden)

    Jyotika Bahuguna

    2015-04-01

    Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

  7. Existence and control of Go/No-Go decision transition threshold in the striatum.

    Science.gov (United States)

    Bahuguna, Jyotika; Aertsen, Ad; Kumar, Arvind

    2015-04-01

    A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

  8. 5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

    Science.gov (United States)

    Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

    2017-03-01

    Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. Identification of Functional Clusters in the Striatum Using Infinite Relational Modeling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Madsen, Kristoffer Hougaard; Siebner, Hartwig

    2011-01-01

    In this paper we investigate how the Infinite Relational Model can be used to infer functional groupings of the human striatum using resting state fMRI data from 30 healthy subjects. The Infinite Relational Model is a non-parametric Bayesian method for infering community structure in complex netw...... and non-links in the graphs as missing. We find that the model is performing well above chance for all subjects....

  10. Differences between Neural Activity in Prefrontal Cortex and Striatum during Learning of Novel Abstract Categories

    OpenAIRE

    Antzoulatos, Evan G.; Miller, Earl K.

    2011-01-01

    Learning to classify diverse experiences into meaningful groups, like categories, is fundamental to normal cognition. To understand its neural basis, we simultaneously recorded from multiple electrodes in the lateral prefrontal cortex and dorsal striatum, two interconnected brain structures critical for learning. Each day, monkeys learned to associate novel, abstract dot-based categories with a right vs. left saccade. Early on, when they could acquire specific stimulus-response associations, ...

  11. A common currency for the computation of motivational values in the human striatum

    Science.gov (United States)

    Li, Yansong; Dreher, Jean-Claude

    2015-01-01

    Reward comparison in the brain is thought to be achieved through the use of a ‘common currency’, implying that reward value representations are computed on a unique scale in the same brain regions regardless of the reward type. Although such a mechanism has been identified in the ventro-medial prefrontal cortex and ventral striatum in the context of decision-making, it is less clear whether it similarly applies to non-choice situations. To answer this question, we scanned 38 participants with fMRI while they were presented with single cues predicting either monetary or erotic rewards, without the need to make a decision. The ventral striatum was the main brain structure to respond to both cues while showing increasing activity with increasing expected reward intensity. Most importantly, the relative response of the striatum to monetary vs erotic cues was correlated with the relative motivational value of these rewards as inferred from reaction times. Similar correlations were observed in a fronto-parietal network known to be involved in attentional focus and motor readiness. Together, our results suggest that striatal reward value signals not only obey to a common currency mechanism in the absence of choice but may also serve as an input to adjust motivated behaviour accordingly. PMID:24837478

  12. Efferent projections of the dorsal ventricular ridge and the striatum in the Tegu lizard. Tupinambis nigropunctatus.

    Science.gov (United States)

    Voneida, T J; Sligar, C M

    1979-07-01

    A H3 proline-leucine mixture was injected into the dorsal ventricular ridge (DVR) and striatum of the Tegu lizard in order to determine their efferent projections. The brains were processed according to standard radioautographic technique, and counterstained with cresyl violet. DVR projections were generally restricted to the telencephalon, while striatal projections were limited to diencephalic and mesencephalic structures. Thus the anterior DVR projects ipsilaterally to nuclei sphericus and lateralis amygdalae, striatum (ipsilateral and contralateral) ventromedial nucleus of the hypothalamus, nucleus accumbens, anterior olfactory nucleus, nucleus of the lateral olfactory tract and lateral pallium. Posterior DVR projections enter ipsilateral anterior olfactory nucleus, lateral and interstitial amygdalar nuclei, olfactory tubercle and bulb, nucleus of the lateral olfactory tract and a zone surrounding the ventromedial hypothalamic nucleus. Labeled axons from striatal injections pass caudally in the lateral forebrain bundle to enter (via dorsal peduncle) nuclei dorsomedialis, medialis posterior, entopeduncularis anterior, and a zone surrounding nucleus rotundus. Others join the ventral peduncle of LFB and enter ventromedial nucleus (thalami), while the remaining fibers continue caudally in the ventral peduncle to the mesencephalic prerubral field, central gray, substantia nigra, nucleus intercollicularis, reticular formation and pretectal nucleus posterodorsalis. These results are discussed in relation to the changing notions regarding terminology, classification and functions of dorsl ventricular ridge and striatum.

  13. Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

    Science.gov (United States)

    Kishida, Kenneth T.; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R.; Laxton, Adrian W.; Tatter, Stephen B.; White, Jason P.; Ellis, Thomas L.; Phillips, Paul E. M.; Montague, P. Read

    2016-01-01

    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons. PMID:26598677

  14. Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

    Science.gov (United States)

    Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

    2016-01-01

    The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

  15. Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

    Directory of Open Access Journals (Sweden)

    Christina Coughlan

    2015-01-01

    Full Text Available Epidemiological studies indicate exposures to the herbicide paraquat (PQ and fungicide maneb (MB are associated with increased risk of Parkinson’s disease (PD. Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg, MB (30 mg/kg, or the combination of PQ and MB (PQMB. Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

  16. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    International Nuclear Information System (INIS)

    Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

    2002-01-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  17. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

    2002-04-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  18. Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

    Science.gov (United States)

    Hoffmann, Hanne Mette; Crouzin, Nadine; Moreno, Estefanía; Raivio, Noora; Fuentes, Silvia; McCormick, Peter J.; Vignes, Michel

    2017-01-01

    Abstract Background: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise. Methods: We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission. Results: We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein. Interestingly, the group I metabotropic glutamate receptor antagonist/inverse-agonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride, led to a specific increase in cAMP responsive-element binding protein phosphorylation after chronic cocaine self-administration, specifically in the nucleus accumbens, but not in the striatum. Conclusions: Prolonged cocaine self-administration, through withdrawal, leads to a blunting of group I metabotropic glutamate receptor

  19. A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

    Science.gov (United States)

    McDonald, Robert J; Jones, Jana; Richards, Blake; Hong, Nancy S

    2006-09-01

    The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

  20. Early evolution and recovery from excitotoxic injury in the neonatal rat brain

    NARCIS (Netherlands)

    Lookeren Campagne, van M.; Verheul, H.B.; Nicolaij, K.; Balázs, R.E.

    1994-01-01

    We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a

  1. [Research for dependablity of administration of platycodi radix in Tianwang Buxinwan decoction with change of brain inhibitive neurotransmitte in rats by microdialysis].

    Science.gov (United States)

    Liu, Ping; He, Xin-rong; Zhou, Wen-bin; Shen, Ran-ran; Feng, Fan

    2008-12-01

    To study the effects of Tianwang Buxinwan decoction on the contents of amino acids neurotransmitters in corpus striatum of rats to implicate the mechanism of Tianwang Buxinwan promoting and Improving sleeping. Contents of two amino acids neurotransmitters in corpus striatum of rats were prepared by microdialysis technology and were determined by HPLC which involved pre-column derivation with orthophthaladehyde, recersed-phase gradient elution and fluorescence detection. In the experimental separation condition, Tianwang Buxinwan seemed do not influence three kinds of contents of amino acids neurotransmiters (glutamic acid, glycin, aspartic acid), but TBW seemed increase the content of gamma-GABA in corpus striatum of rats. The effects of Tianwang Buxinwan to relieve uneasiness may relate with the inhibitory amino acids gamma-GABA. Tianwang Buxinwan may promote increasing the content of gamma-GABA. This discovery may be helpful for the deep study of related mechanism of Tianwang Buxinwan.

  2. Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

    International Nuclear Information System (INIS)

    Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

    2008-01-01

    Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

  3. Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

    Energy Technology Data Exchange (ETDEWEB)

    Kienast, Thorsten; Rapp, Michael [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias [University of Mainz, Department of Nuclear Medicine, Mainz (Germany); Wrase, Jana; Heinz, Andreas [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Central Institute of Mental Health, Mannheim (Germany); Braus, Dieter F. [University of Hamburg, Neuroimage Nord, Department of Psychiatry, Hamburg (Germany); Smolka, Michael N.; Mann, Karl [Central Institute of Mental Health, Mannheim (Germany); Roesch, Frank [University of Mainz, Institute of Nuclear Chemistry, Mainz (Germany); Cumming, Paul [PET Center and Center for Functionally Integrative Neuroscience, Aarhus (Denmark); Gruender, Gerhard [Aachen University Medical Center, Department of Psychiatry of the RWTH, Mainz (Germany); Bartenstein, Peter [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

    2008-06-15

    Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [{sup 18}F]DOPA for measurements of dopamine synthesis capacity and [{sup 18}F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [{sup 18}F]DOPA net influx constant K{sub in}{sup app} /[{sup 18}F]DMFP-binding potential (BP{sub N}D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

  4. Functional inactivation of dorsal medial striatum alters behavioral flexibility and recognition process in mice.

    Science.gov (United States)

    Qiao, Yanhua; Wang, Xingyue; Ma, Lian; Li, Shengguang; Liang, Jing

    2017-10-01

    Deficits in behavioral flexibility and recognition memory are commonly observed in mental illnesses and neurodegenerative diseases. Abnormality of the striatum has been implicated in an association with the pathology of these diseases. However, the exact roles of striatal heterogeneous structures in these cognitive functions are still unknown. In the present study, we investigated the effects of suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus accumbens core (NAcC) on reversal learning and novelty recognition in mice. In addition, the locomotor activity, anxiety-like behavior and social interaction were analyzed. Neuronal inactivation was performed by expressing lentivirus-mediated tetanus toxin (TeNT) in the target regions. The results showed that reversal learning was facilitated by neuronal inactivation in the DMStr but not the NAcC, which was attributable to accelerated extinction of acquired strategy but not to impaired memory retention. Furthermore, mice with NAcC inactivation spent more time exploring a novel object than a familiar one, comparable to control mice. In contrast, mice with DMStr inactivation exhibited no preference to a novel environment during the novel object or place recognition test. The DMStr mice also exhibited decreased anxiety level. No phenotypic effect was observed in the locomotion or social interaction in mice with either DMStr or NAcC inactivation. Altogether, these findings suggest that the DMStr but not the ventral area of the striatum plays a crucial role in learning and memory by coordinating spatial exploration as well as mediating information updating. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  6. Goal- and retrieval-dependent activity in the striatum during memory recognition.

    Science.gov (United States)

    Clos, Mareike; Schwarze, Ulrike; Gluth, Sebastian; Bunzeck, Nico; Sommer, Tobias

    2015-06-01

    The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions. To examine whether striatal activity during memory recognition reflects subjective value indeed, we conducted an fMRI study using a recognition memory paradigm in which the participants rated not only the recognition confidence but also indicated the pleasantness associated with the previous memory retrieval. The results demonstrated a high positive correlation between confidence and pleasantness both on the behavioral and brain activation level particularly in the striatum. As almost all of variance in the striatal confidence signal could be explained by experienced pleasantness, this part of the striatal memory recognition response probably corresponds to greater subjective value of high confidence responses. While perceived oldness was also strongly correlated with striatal activity, this activation pattern was clearly distinct from that associated with confidence and pleasantness and thus could not be explained by higher subjective value to detect "old" items. Together, these results show that at least two independent processes contribute to striatal activation in recognition memory: a more flexible evaluation response dependent on context and goals captured by memory confidence and a potentially retrieval-related response captured by perceived oldness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  8. Abnormal air righting behaviour in the spontaneously hypertensive rat model of ADHD

    OpenAIRE

    Dommett, Eleanor J; Rostron, Claire L

    2011-01-01

    The spontaneously hypertensive rat (SHR) is the most commonly used model of attention-deficit hyperactivity disorder (ADHD), displaying the main symptoms of the disorder which are responsive to psychostimulant treatments. Research to date has focused on behavioural tests investigating functioning of the striatum or prefrontal cortex in these rats. However, there is now evidence that the superior colliculus, a structure associated with head and eye movements, may also be dysfunctional in ADHD....

  9. Vasogenic edema in striatum following ingestion of glufosinate-containing herbicide.

    Science.gov (United States)

    Lee, Hui-Young; Song, Seo-Young; Lee, Seung-Hwan; Lee, Seo-Young; Kim, Sung-Hun; Ryu, Sook-Won

    2009-10-01

    Glufosinate-ammonium (GLA) is a broad-spectrum herbicide used worldwide. We report a patient who attempted suicide by ingesting a liquid herbicide containing GLA. A diffusion-weighted MRI showed cytotoxic edema in the hippocampus as well as vasogenic edema in the striata. To our knowledge, vasogenic edema caused by GLA-containing herbicide involving the striatum has not been reported in association with cytotoxic edema in the hippocampus. We assume that this herbicide affected the central nervous system via different mechanisms to produce both cytotoxic and vasogenic edema in the same patient.

  10. Sexual dimorphism in song-induced ZENK expression in the medial striatum of juvenile zebra finches

    OpenAIRE

    Bailey, David J.; Wade, Juli

    2006-01-01

    In the brains of male zebra finches (Taeniopygia guttata), the nuclei that direct song learning and production are larger than the corresponding regions in females, who do not sing. The dimorphism in Area X of the medial striatum (MSt), an area important for song learning, is even more dramatic in that it is identifiable in males but not females by Nissl stain. In the present study, conspecific song, but not other auditory stimuli, induced expression of the immediate early gene ZENK in the MS...

  11. The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum.

    Science.gov (United States)

    Brenes, Juan C; Fornaguera, Jaime

    2009-03-02

    This study examined the effect of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, on isolation-induced changes on sucrose consumption and preference, spontaneous open-field activity, forced swimming behavior, and on tissue levels of 5-HT and dopamine (DA) in hippocampus and ventral striatum (VS). Male Sprague-Dawley rats were reared in social isolation or group housing from postnatal day 28. Thirty-two days later, half of the isolated animals were orally treated with fluoxetine (10mg/kg/day) during the following 34 days. At the end of this period, behavior was assessed and afterward ex-vivo tissue samples were obtained. It was found that fluoxetine restored isolation-increased sucrose consumption and immobility behavior, without affecting locomotor activity, which appeared slightly increased in isolated groups both treated and untreated. In the hippocampus, isolation rearing depleted 5-HT contents and increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels, as well as 5-HT and DA turnover. These neurochemical alterations were reversed by fluoxetine. In VS, treated and untreated isolated rats showed higher 5-HT levels than grouped congeners. Although fluoxetine did not affect 5-HT and DA contents in this region, it slightly reversed the alterations in the 5-HT and DA turnover observed in isolated rats. Overall, social isolation impaired incentive and escape motivated behaviors. At the neurochemical level, isolation rearing affected 5-HT rather than DA activity, and this differential effect was more noticeable in hippocampus than in VS. The chronic treatment with fluoxetine during the last month of rearing somewhat prevented these behavioral and neurochemical alterations. Our data suggest that isolation rearing is an appropriate procedure to model some developmental-related alterations underlying depression disorders.

  12. Distinct changes in CREB phosphorylation in frontal cortex and striatum during contingent and non-contingent performance of a visual attention task

    Directory of Open Access Journals (Sweden)

    Mirjana eCarli

    2011-10-01

    Full Text Available The cyclic-AMP response element binding protein (CREB family of transcription factors has been implicated in numerous forms of behavioural plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC and dorsal (caudate putamen, CPu and ventral (nucleus accumbens, NAC striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, master, a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, yoked and a control group matched for food deprivation and exposure to the test apparatus (untrained. Rats trained on the 5-CSRTT (both master and yoked had higher levels of CREB protein in the FC, CPu and NAC compared to untrained controls. Despite the divergent behaviour of master and yoked rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (master, CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (yoked. The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

  13. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2018-02-01

    Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

  14. Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

    Science.gov (United States)

    Mattfeld, Aaron T.; Stark, Craig E. L.

    2015-01-01

    The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

  15. Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET

    International Nuclear Information System (INIS)

    Iyo, Masaomi; Yamasaki, Toshiro; Fukuda, Hiroshi

    1989-01-01

    The effect of aging on 11 C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The ll normal volunteers (22 to 72 years old) participated in this study. The uptake of 11 C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11 C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant 'k 3 ' was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k 3 value with aging was observed. The k 3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum. (author)

  16. 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

  17. The role of the dorsal striatum in extinction: A memory systems perspective.

    Science.gov (United States)

    Goodman, Jarid; Packard, Mark G

    2018-04-01

    The present review describes a role for the dorsal striatum in extinction. Evidence from brain lesion and pharmacological studies indicate that the dorsolateral region of the striatum (DLS) mediates extinction in various maze learning and instrumental learning tasks. Within the context of a multiple memory systems view, the role of the DLS in extinction appears to be selective. Specifically, the DLS mediates extinction of habit memory and is not required for extinction of cognitive memory. Thus, extinction mechanisms mediated by the DLS may involve response-produced inhibition (e.g. inhibition of existing stimulus-response associations or formation of new inhibitory stimulus-response associations), as opposed to cognitive mechanisms (e.g. changes in expectation). Evidence also suggests that NMDA-dependent forms of synaptic plasticity may be part of the mechanism through which the DLS mediates extinction of habit memory. In addition, in some learning situations, DLS inactivation enhances extinction, suggesting a competitive interaction between multiple memory systems during extinction training. Consistent with a multiple memory systems perspective, it is suggested that the DLS represents one of several distinct neural systems that specialize in extinction of different kinds of memory. The relevance of these findings to the development of behavioral and pharmacological therapies that target the maladaptive habit-like symptoms in human psychopathology is also briefly considered. Published by Elsevier Inc.

  18. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2017-05-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

  19. Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

    Science.gov (United States)

    Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

    2011-12-01

    Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

  20. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  1. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure.

    Directory of Open Access Journals (Sweden)

    Ju Hwan Kim

    Full Text Available The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs. EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF of 835 MHz at a specific absorption rate (SAR of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress.

  2. Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and Primate Striatum Activity

    Directory of Open Access Journals (Sweden)

    Ioan eOpris

    2011-05-01

    Full Text Available Although reward probability is an important factor that shapes animal behavior, it is not well understood however, how the primate brain translates reward expectation into the vigor of movement (reaction time and speed. To address this question, we trained two monkeys in a reaction time task that required wrist movements in response to vibrotactile and visual stimuli, with a variable reward schedule. Correct performance was rewarded in 75 % of the trials. Monkeys were certain that they would be rewarded only in the trials immediately following withheld rewards. In these trials, the animals responded sooner and moved faster. Single-unit recordings from the dorsal striatum revealed that modulations in striatal neurons reflected such modulations of movement vigor. First, in the trials with certain rewards, striatal neurons modulated their firing rates earlier. Second, magnitudes of changes in neuronal firing rates depended on whether or not monkeys were certain about the reward. Third, these modulations depended on the sensory modality of the cue (visual vs. vibratory and/or movement direction (flexions vs. extensions. We conclude that dorsal striatum may be a part of the mechanism responsible for the modulation of movement vigor in response to changes of reward predictability.

  3. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

    Science.gov (United States)

    Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

    2008-04-01

    Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

  4. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  5. Antioxidant responses and photosynthetic behaviors of Kappaphycus alvarezii and Kappaphycus striatum (Rhodophyta, Solieriaceae) during low temperature stress.

    Science.gov (United States)

    Li, Hu; Liu, Jianguo; Zhang, Litao; Pang, Tong

    2016-12-01

    Kappaphycus are farmed in tropical countries as raw material for carrageenan, which is widely used in food industry. The sea area available for farming is one limiting factor in the production of seaweeds. Though cultivation is spreading into subtropical regions, the lower seawater temperature is an important problem encountered in subtropical regions for the farming of Kappaphycus. This research of physiological response to low temperature stress will be helpful for screening Kappaphycus strains for growth in a lower temperature environment. Responses of antioxidant systems and photosystem II (PSII) behaviors in Kappaphycus alvarezii and Kappaphycus striatum were evaluated during low temperature treatments (23, 20, 17 °C). Compared with the controls at 26 °C, the H 2 O 2 concentrations increased in both species when the thalli were exposed to low temperatures (23, 20, 17 °C), but these increases were much greater in K. striatum than in K. alvarezii thalli, suggesting that K. striatum suffered more oxidative stress. The activities of some important antioxidant enzymes (e.g. superoxide dismutase and ascorbate peroxidase) and the hydroxyl free radical scavenging capacity were substantially higher at 23, 20 and 17 °C than at the control 26 °C in K. alvarezii, indicating that the antioxidant system of K. alvarezii enhanced its resistance to low temperature. However, no significant increases of antioxidant enzymes activities were observed at 20 and 17 °C in K. striatum. In addition, both the maximal efficiency of PSII photochemistry (F V /F m ) and the performance index (PI ABS ) decreased significantly in K. striatum at 23 °C, indicating that the photosynthetic apparatus was damaged at 23 °C. In contrast, no significant decreases of either F V /F m or PI ABS were observed in K. alvarezii at 23 °C. It is concluded that K. alvarezii has greater tolerance to low temperature than K. striatum.

  6. Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Luciane B. Ceretta

    2012-01-01

    Full Text Available Diabetes Mellitus (DM is associated with pathological changes in the central nervous system (SNC as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg, and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD, and catalase (CAT were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals’ recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

  7. Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

    DEFF Research Database (Denmark)

    Cumming, P; Danielsen, E H; Vafaee, M

    2001-01-01

    , both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers...... for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However...

  8. Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25{+-}2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% {+-} 1.3% and 10.6% {+-} 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% {+-} 4.5% vs. 6.6% {+-} 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release.

  9. Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25±2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% ± 1.3% and 10.6% ± 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% ± 4.5% vs. 6.6% ± 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release

  10. Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Science.gov (United States)

    Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

    2015-01-01

    17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease. PMID:26074768

  11. Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.

    Science.gov (United States)

    Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

    2015-01-01

    17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  12. Endogenous 17ß-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Directory of Open Access Journals (Sweden)

    Alessandro eTozzi

    2015-05-01

    Full Text Available 17β-estradiol (E2, a neurosteroid synthesized by P450-aromatase (ARO, modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs and dopamine (DA receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP in both medium spiny neurons (MSNs and cholinergic interneurons (ChIs. Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  13. Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

    Science.gov (United States)

    Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

    2011-01-01

    The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

  14. INCREASES IN FUNCTIONAL CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND STRIATUM DURING CATEGORY LEARNING

    Science.gov (United States)

    Antzoulatos, Evan G.; Miller, Earl K.

    2014-01-01

    SUMMARY Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is thought critical for cognition, and has been linked to conditions like autism and schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys acquired new categories. Category learning was accompanied by an increase in beta-band synchronization of LFPs between, but not within, the PFC and STR. After learning, different pairs of PFC-STR electrodes showed stronger synchrony for one or the other category, suggesting category-specific functional circuits. This category-specific synchrony was also seen between PFC spikes and STR LFPs, but not the reverse, reflecting the direct monosynaptic connections from the PFC to STR. However, causal connectivity analyses suggested that the polysynaptic connections from STR to the PFC exerted a stronger overall influence. This supports models positing that the basal ganglia “train” the PFC. Category learning may depend on the formation of functional circuits between the PFC and STR. PMID:24930701

  15. Learning multiple variable-speed sequences in striatum via cortical tutoring.

    Science.gov (United States)

    Murray, James M; Escola, G Sean

    2017-05-08

    Sparse, sequential patterns of neural activity have been observed in numerous brain areas during timekeeping and motor sequence tasks. Inspired by such observations, we construct a model of the striatum, an all-inhibitory circuit where sequential activity patterns are prominent, addressing the following key challenges: (i) obtaining control over temporal rescaling of the sequence speed, with the ability to generalize to new speeds; (ii) facilitating flexible expression of distinct sequences via selective activation, concatenation, and recycling of specific subsequences; and (iii) enabling the biologically plausible learning of sequences, consistent with the decoupling of learning and execution suggested by lesion studies showing that cortical circuits are necessary for learning, but that subcortical circuits are sufficient to drive learned behaviors. The same mechanisms that we describe can also be applied to circuits with both excitatory and inhibitory populations, and hence may underlie general features of sequential neural activity pattern generation in the brain.

  16. Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report

    Directory of Open Access Journals (Sweden)

    Zangana Hero M

    2011-07-01

    Full Text Available Abstract Background Bilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse. Case presentation We report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission. Conclusion This is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

  17. From the ventral to the dorsal striatum: devolving views of their roles in drug addiction.

    Science.gov (United States)

    Everitt, Barry J; Robbins, Trevor W

    2013-11-01

    We revisit our hypothesis that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntarily drug use to habitual, and ultimately compulsive drug use. We especially focus on the transitions in striatal control over drug seeking behaviour that underlie these transitions since functional heterogeneity of the striatum was a key area of Ann Kelley's research interests and one in which she made enormous contributions. We also discuss the hypothesis in light of recent data that the emergence of a compulsive drug seeking habit both reflects a shift to dorsal striatal control over behaviour and impaired prefontal cortical inhibitory control mechanisms. We further discuss aspects of the vulnerability to compulsive drug use and in particular the impact of impulsivity. In writing this review we acknowledge the untimely death of an outstanding scientist and a dear personal friend. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The PDE10A inhibitor MP-10 and haloperidol produce distinct gene expression profiles in the striatum and influence cataleptic behavior in rodents.

    Science.gov (United States)

    Gentzel, Renee C; Toolan, Dawn; Roberts, Rhonda; Koser, Amy Jo; Kandebo, Monika; Hershey, James; Renger, John J; Uslaner, Jason; Smith, Sean M

    2015-12-01

    Phosphodiesterase 10A (PDE10A) has garnered attention as a potential therapeutic target for schizophrenia due to its prominent striatal expression and ability to modulate striatal signaling. The present study used the selective PDE10A inhibitor MP-10 and the dopamine D2 antagonist haloperidol to compare effects of PDE10A inhibition and dopamine D2 blockade on striatopallidal (D2) and striatonigral (D1) pathway activation. Our studies confirmed that administration of MP-10 significantly elevates expression of the immediate early genes (IEG) c-fos, egr-1, and arc in rat striatum. Furthermore, we demonstrated that MP-10 induced egr-1 expression was distributed evenly between enkephalin-containing D2-neurons and substance P-containing D1-neurons. In contrast, haloperidol (3 mg/kg) selectively activated egr-1 expression in enkephalin neurons. Co-administration of MP-10 and haloperidol (0.5 mg/kg) increased IEG expression to a greater extent than either compound alone. Similarly, in a rat catalepsy assay, administration of haloperidol (0.5 mg/kg) or MP-10 (3-30 mg/kg) did not produce cataleptic behavior when dosed alone, but co-administration of haloperidol with MP-10 (3 and 10 mg/kg) induced cataleptic behaviors. Interestingly, co-administration of haloperidol with a high dose of MP-10 (30 mg/kg) failed to produce cataleptic behavior. These findings are important for understanding the neural circuits involved in catalepsy and suggest that the behavioral effects produced by PDE10A inhibitors may be influenced by concomitant medication and the level of PDE10A inhibition achieved by the dose of the inhibitor. Copyright © 2015. Published by Elsevier Ltd.

  19. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    Directory of Open Access Journals (Sweden)

    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  20. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

    DEFF Research Database (Denmark)

    Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

    2013-01-01

    Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

  1. Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

    2012-01-01

    DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

  2. Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

    2012-02-15

    DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

  3. Control of Huntington’s Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2

    Directory of Open Access Journals (Sweden)

    Lea J. Hachigian

    2017-12-01

    Full Text Available Summary: Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington’s disease (HD. The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT. Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes that present additional targets for normalization of corticostriatal dysfunction in HD. : Hachigian et al. demonstrate that manipulating levels of the striatum-enriched transcription factor Foxp2 can either rescue or mimic HD-associated behaviors in vivo. They link Foxp2 to the post-developmental regulation of the structure and function of the corticostriatal synapse. Keywords: Huntington’s disease, Foxp2, striatum, corticostriatal synapse

  4. Amphetamine-enhanced accumulation of [3H]-spiperone in mouse corpus striatum in vivo: Modification by other drugs

    International Nuclear Information System (INIS)

    Dorris, R.L.

    1989-01-01

    Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with [ 3 H]-spiperone (20 μCi/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before [ 3 H]-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by α - methyltyrosine (α-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of [ 3 H]-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by α-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release

  5. Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

    NARCIS (Netherlands)

    Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Fenske, Sabrina; Schirmbeck, Frederike; Englisch, Susanne; Schilling, Claudia; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2015-01-01

    Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be

  6. Topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus).

    Science.gov (United States)

    Ashwell, K W S

    2008-09-01

    The topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus) have been studied using Nissl staining in conjunction with myelin staining, enzyme reactivity to acetylcholinesterase and NADPH diaphorase, and immunoreactivity to parvalbumin, calbindin, calretinin, tyrosine hydroxylase, neuropeptide Y, and neurofilament protein (SMI-32 antibody). All those components of the striatum and pallidum found in eutherian mammals could also be identified in the echidna's brain, with broad chemoarchitectural similarities to those regions in eutherian brains also apparent. There was a clear chemoarchitectural gradient visible with parvalbumin immunoreactivity of neurons and fibers, suggesting a subdivision of the echidna caudatoputamen into weakly reactive rostrodorsomedial and strongly reactive caudoventrolateral components. This may, in turn, relate to subdivision into associative versus sensorimotor CPu and reflect homology to the caudate and putamen of primates. Moreover, the chemoarchitecture of the echidna striatum suggested the presence of striosome-matrix architecture. The morphology of identified neuronal groups (i.e., parvalbumin, calbindin, and neuropeptide Y immunoreactive) in the echidna striatum and pallidum showed many similarities to those seen in eutherians, although the pattern of distribution of calbindin immunoreactive neurons was more uniform in the caudatoputamen of the echidna than in therians. These observations indicate that the same broad features of striatal and pallidal organization apply across all mammals and suggest that these common features may have arisen before the divergence of the monotreme and therian lineages.

  7. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  8. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    Directory of Open Access Journals (Sweden)

    Hiroaki Kawamichi

    2016-11-01

    Full Text Available Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68. Furthermore, we also conducted a voxel-based morphometry (VBM study of the effects of being in a romantic relationship (N = 113. Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

  9. Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats

    Science.gov (United States)

    Lotan, Dafna; Benhar, Itai; Alvarez, Kathy; Mascaro-Blanco, Adita; Brimberg, Lior; Frenkel, Dan; Cunningham, Madeleine W.; Joel, Daphna

    2014-01-01

    Group A β-hemolytic streptococcal (GAS) infection is associated with a spectrum of neuropsychiatric disorders. The leading hypothesis regarding this association proposes that a GAS infection induces the production of auto-antibodies, which cross-react with neuronal determinants in the brain through the process of molecular mimicry. We have recently shown that exposure of rats to GAS antigen leads to the production of anti-neuronal antibodies concomitant with the development of behavioral alterations. The present study tested the causal role of the antibodies by assessing the behavior of naïve rats following passive transfer of purified antibodies from GAS-exposed rats. Immunoglobulin G (IgG) purified from the sera of GAS-exposed rats was infused directly into the striatum of naïve rats over a 21-day period. Their behavior in the induced-grooming, marble burying, food manipulation and beam walking assays was compared to that of naïve rats infused with IgG purified from adjuvant-exposed rats as well as of naïve rats. The pattern of in vivo antibody deposition in rat brain was evaluated using immunofluorescence and colocalization. Infusion of IgG from GAS-exposed rats to naïve rats led to behavioral and motor alterations partially mimicking those seen in GAS-exposed rats. IgG from GAS-exposed rats reacted with D1 and D2 dopamine receptors and 5HT-2A and 5HT-2C serotonin receptors in vitro. In vivo, IgG deposits in the striatum of infused rats colocalized with specific brain proteins such as dopamine receptors, the serotonin transporter and other neuronal proteins. Our results demonstrate the potential pathogenic role of autoantibodies produced following exposure to GAS in the induction of behavioral and motor alterations, and support a causal role for autoantibodies in GAS-related neuropsychiatric disorders. PMID:24561489

  10. Comparison between dopamine-stimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum

    International Nuclear Information System (INIS)

    Andersen, P.H.; Groenvald, F.C.; Jansen, J.A.

    1985-01-01

    Methods for measuring 3 H-SCH 23990 binding and dopamine (DA) stimulated adenylate cyclase (AC) were established in identical tissue preparations and under similar experimental conditions. Pharmacological characterization revealed that both assays involved interaction with the D1 receptor or closely associated sites. In order to investigate whether the binding sites for 3 H-SCH 23390 and DA in fact are identical, the antagonistic effects of a variety of pharmacologically active compounds were examined. Surprisingly, the K/sub i/-values obtained from Schild-plot analysis of the antagonism of DA-stimulated AC, were 80-240 times higher than the K/sub i/-values obtained from competition curves of 3 H-SCH 23390 binding. Since both assays were performed under identical conditions, the differences in K/sub i/-values indicate the possibility of different binding sites for DA and 3 H-SCH 23390 or, that DA and 3 -SCH 23390 label different states of the same receptor. 19 references, 7 figures, 2 tables

  11. Region-specific differences in bioenergetic proteins and protein response to acute high fat diet in brains of low and high capacity runner rats.

    Science.gov (United States)

    Gan, Li; Ma, Delin; Li, Min; Yang, Fu-Chen; Rogers, Robert S; Wheatley, Joshua L; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C; Stanford, John A

    2018-05-01

    Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions. LCR rats exhibited lower levels of mitochondrial proteins (PGC1-α, Nrf-1, TFAM), and greater p-AMPK, in striatum, but not in the other brain regions. Mitochondrial protein levels were greater in HFD LCR striatum, while p-AMPK was lower in this group. Markers of lower mitochondrial biogenesis and increased metabolic demand were limited to the LCR striatum, which nevertheless maintained the capacity to respond to an acute HFD challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Dejanović Bratislav

    2015-01-01

    Full Text Available The present study was directed to potentially beneficial effects of agmatine (AGM on oxidative/nitrosative stress development in selective vulnerable brain regions during chlorpromazine (HPZ treatment in rats. All tested compounds were administered intraperitoneally (i.p. in one single dose. The animals were divided into control (K, 0.9 % saline solution, HPZ (HPZ, 38.7 mg/kg b.w., HPZ+AGM (AGM, 75 mg/kg b.w. immediately after HPZ, 38.7 mg/kg b.w. i.p. and AGM (AGM, 75 mg/kg b.w. groups. Rats were sacrificed by decapitation 24 hours after the treatment. Analysis of data showed that HPZ+AGM injection significantly decreased drug concentration compared with HPZ-animals (p<0.05. HPZ application increased lipid peroxidation (p<0.001 in cortex, striatum and hippocampus, nitrite and nitrate concentration (p<0.001 in all three brain regions and superoxide anion production (p<0.05 in all three brain structures, while completely damaged enzymatic antioxidative defense system (superoxide dismutase in both cortex and striatum p<0.05 and hippocampus p<0.001; glutathion reductase in both cortex and striatum p<0.001 and hippocampus p<0.05; catalase in cortex p<0.001 and both striatum and hippocampus p<0.05. However, treatment with AGM significantly attenuated the oxidative stress parameters compared to HPZ-group (lipid peroxidation in cortex p<0.001, striatum p<0.01 and hippocampus p<0.05; nitrite and nitrate concentration in all three brain structures p<0.001 and restores antioxidant capacity to control values in all examined brain structures. Immunohistochemical staining of GFAP molecules in rats showed an increase in the number of positive cells 24 h after acute HPZ-administration. All these results indicate that AGM may be effective in the protection of HPZ-induced brain injury in rats.

  13. Attenuation of arsenic neurotoxicity by curcumin in rats

    International Nuclear Information System (INIS)

    Yadav, Rajesh S.; Sankhwar, Madhu Lata; Shukla, Rajendra K.; Chandra, Ramesh; Pant, Aditya B.; Islam, Fakhrul; Khanna, Vinay K.

    2009-01-01

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  14. [Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

    Science.gov (United States)

    V'iushina, A V; Pritvorova, A V; Flerov, M A

    2012-08-01

    We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

  15. Locomotor activity and catecholamine receptor binding in adult normotensive and spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Hellstrand, K.; Engel, J.

    1980-01-01

    The binding of 3 H-WB 4101, an α 1 -adrenoceptor antagonist, the membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of 3 H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of 3 H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a disfunction in the noradrenergic neurons in the central nervous system. (author)

  16. Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex.

    Science.gov (United States)

    Dere, E; Zheng-Fischhöfer, Q; Viggiano, D; Gironi Carnevale, U A; Ruocco, L A; Zlomuzica, A; Schnichels, M; Willecke, K; Huston, J P; Sadile, A G

    2008-05-02

    Neuronal gap junctions in the brain, providing intercellular electrotonic signal transfer, have been implicated in physiological and behavioral correlates of learning and memory. In connexin31.1 (Cx31.1) knockout (KO) mice the coding region of the Cx31.1 gene was replaced by a LacZ reporter gene. We investigated the impact of Cx31.1 deficiency on open-field exploration, the behavioral response to an odor, non-selective attention, learning and memory performance, and the levels of memory-related proteins in the hippocampus, striatum and the piriform cortex. In terms of behavior, the deletion of the Cx31.1 coding DNA in the mouse led to increased exploratory behaviors in a novel environment, and impaired one-trial object recognition at all delays tested. Despite strong Cx31.1 expression in the peripheral and central olfactory system, Cx31.1 KO mice exhibited normal behavioral responses to an odor. We found increased levels of acetylcholine esterase (AChE) and cAMP response element-binding protein (CREB) in the striatum of Cx31.1 KO mice. In the piriform cortex the Cx31.1 KO mice had an increased heterogeneity of CREB expression among neurons. In conclusion, gap-junctions featuring the Cx31.1 protein might be involved in open-field exploration as well as object memory and modulate levels of AChE and CREB in the striatum and piriform cortex.

  17. A common neural code for social and monetary rewards in the human striatum.

    Science.gov (United States)

    Wake, Stephanie J; Izuma, Keise

    2017-10-01

    Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re-analyzed the original data and addressed this question using multivariate-pattern-analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing. © The Author (2017). Published by Oxford University Press.

  18. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

    Science.gov (United States)

    Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2017-01-01

    Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

  19. Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

    Directory of Open Access Journals (Sweden)

    Ulrich eKirk

    2015-02-01

    Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

  20. Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

    Science.gov (United States)

    Torres, Carmen; Glueck, Amanda C; Conrad, Shannon E; Morón, Ignacio; Papini, Mauricio R

    2016-09-22

    The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

    Science.gov (United States)

    Holz, Nathalie E; Boecker-Schlier, Regina; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2017-02-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

    Science.gov (United States)

    Luan, Yanan; Ren, Xiangpeng; Zheng, Wu; Zeng, Zhenhai; Guo, Yingzi; Hou, Zhidong; Guo, Wei; Chen, Xingjun; Li, Fei; Chen, Jiang-Fan

    2018-01-01

    Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

  3. Interest in politics modulates neural activity in the amygdala and ventral striatum.

    Science.gov (United States)

    Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

    2010-11-01

    Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

  4. Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia.

    Science.gov (United States)

    Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Esslinger, Christine; Schilling, Claudia; Schirmbeck, Frederike; Englisch, Susanne; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2014-07-01

    Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

    Science.gov (United States)

    González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

    2013-10-25

    Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

  6. Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia.

    Science.gov (United States)

    Chung, Yu Sun; Barch, Deanna M

    2016-04-01

    Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue-related activations in several regions of the basal ganglia responding to reward-predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. (c) 2016 APA, all rights reserved).

  7. Sequentially switching cell assemblies in random inhibitory networks of spiking neurons in the striatum.

    Science.gov (United States)

    Ponzi, Adam; Wickens, Jeff

    2010-04-28

    The striatum is composed of GABAergic medium spiny neurons with inhibitory collaterals forming a sparse random asymmetric network and receiving an excitatory glutamatergic cortical projection. Because the inhibitory collaterals are sparse and weak, their role in striatal network dynamics is puzzling. However, here we show by simulation of a striatal inhibitory network model composed of spiking neurons that cells form assemblies that fire in sequential coherent episodes and display complex identity-temporal spiking patterns even when cortical excitation is simply constant or fluctuating noisily. Strongly correlated large-scale firing rate fluctuations on slow behaviorally relevant timescales of hundreds of milliseconds are shown by members of the same assembly whereas members of different assemblies show strong negative correlation, and we show how randomly connected spiking networks can generate this activity. Cells display highly irregular spiking with high coefficients of variation, broadly distributed low firing rates, and interspike interval distributions that are consistent with exponentially tailed power laws. Although firing rates vary coherently on slow timescales, precise spiking synchronization is absent in general. Our model only requires the minimal but striatally realistic assumptions of sparse to intermediate random connectivity, weak inhibitory synapses, and sufficient cortical excitation so that some cells are depolarized above the firing threshold during up states. Our results are in good qualitative agreement with experimental studies, consistent with recently determined striatal anatomy and physiology, and support a new view of endogenously generated metastable state switching dynamics of the striatal network underlying its information processing operations.

  8. Inhibition of transcription and translation in the striatum after memory reactivation: Lack of evidence of reconsolidation.

    Science.gov (United States)

    Prado-Alcalá, Roberto A; Medina, Andrea Cristina; Bello-Medina, Paola C; Quirarte, Gina L

    2017-07-01

    It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Dopamine release in ventral striatum during Iowa Gambling Task performance is associated with increased excitement levels in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Møller, Arne; Peterson, Ericka

    2011-01-01

    Aims Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls. Design Pathological Gamblers...... and Healthy Controlswere experimentally compared in a non-gambling (baseline) and gambling condition. Measurements We used Positron Emission Tomography (PET) with the tracer raclopride to measure dopamine D 2/3 receptor availability in the ventral striatum during a non-gambling and gambling condition...... of the Iowa GamblingTask (IGT). After each condition participants rated their excitement level. Setting Laboratory experiment. Participants 18 Pathological Gamblers and 16 Healthy Controls. Findings Pathological Gamblers with dopamine release in the ventral striatum had significantly higher excitement levels...

  10. Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

    DEFF Research Database (Denmark)

    Peterson, Ericka; Gjedde, Albert; Møller, Arne

    Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs...... as reference for all three methods. Mean pB were calculated for left and right putamen, caudate and VST. Correlations between the left and right pB were examined for each striatal region. The results of the three methods were also compared. Results: For all three methods, there was a highly significant...... correlation between the left and right caudate and putamen (pVST (0.01

  11. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

    Science.gov (United States)

    Hamezah, Hamizah Shahirah; Durani, Lina Wati; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Kato, Tomoko; Shiino, Akihiko; Tanaka, Sachiko; Damanhuri, Hanafi Ahmad; Ngah, Wan Zurinah Wan; Tooyama, Ikuo

    2017-12-01

    Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1 H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age. Copyright © 2017. Published by Elsevier Inc.

  12. Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson's rats.

    Science.gov (United States)

    Cho, Han-Sam; Shin, Mal-Soon; Song, Wook; Jun, Tae-Won; Lim, Baek-Vin; Kim, Young-Pyo; Kim, Chang-Ju

    2013-01-01

    Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson's disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. Parkinson's rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson's disease.

  13. Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain

    Science.gov (United States)

    Ferré, S.; Diamond, I.; Goldberg, S.R.; Yao, L.; Hourani, S.M.O.; Huang, Z.L.; Urade, Y.; Kitchen, I.

    2007-01-01

    Adenosine A2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A receptors. A2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A2A receptor knockout mice suggest that A2A receptor antagonists might have some therapeutic potential in pain states, in particular where

  14. Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.

    Science.gov (United States)

    Gross, Joshua D; Kaski, Shane W; Schroer, Adam B; Wix, Kimberley A; Siderovski, David P; Setola, Vincent

    2018-02-01

    Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of administration (sensitization and conditioned place preference) were unaffected, suggesting that RGS12 does not function in support of the rewarding properties of these psychostimulants. To test whether observed response changes upon RGS12 loss were caused by changes to dopamine transporter expression and/or function, we prepared crude membranes from the brains of wild-type and RGS12-null mice and measured dopamine transporter-selective [ 3 H]WIN 35428 binding, revealing an increase in dopamine transporter levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address dopamine transporter function, we prepared striatal synaptosomes and measured [ 3 H]dopamine uptake. Consistent with increased [ 3 H]WIN 35428 binding, dopamine transporter-specific [ 3 H]dopamine uptake in RGS12-null ventral striatal synaptosomes was found to be increased. Decreased amphetamine-induced locomotor activity and increased [ 3 H]WIN 35428 binding were recapitulated with an independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates dopamine transporter expression and function in the ventral striatum, affecting amphetamine- and cocaine-induced increases in dopamine levels that specifically elicit acute hyperlocomotor responses.

  15. The brain cytoplasmic RNA BC1 regulates dopamine D-2 receptor-mediated transmission in the striatum

    OpenAIRE

    Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

    2007-01-01

    Dopamine D-2 receptor (D2DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D-2 receptors in this brain area are essentially obscure. We have studied the physiological responses of the D2DR stimulations in mice...

  16. A multivariate surface-based analysis of the putamen in premature newborns: regional differences within the ventral striatum.

    Directory of Open Access Journals (Sweden)

    Jie Shi

    Full Text Available Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity

  17. The role of the striatum in effort-based decision-making in the absence of reward.

    Science.gov (United States)

    Schouppe, Nathalie; Demanet, Jelle; Boehler, Carsten N; Ridderinkhof, K Richard; Notebaert, Wim

    2014-02-05

    Decision-making involves weighing costs against benefits, for instance, in terms of the effort it takes to obtain a reward of a given magnitude. This evaluation process has been linked to the dorsal anterior cingulate cortex (dACC) and the striatum, with activation in these brain structures reflecting the discounting effect of effort on reward. Here, we investigate how cognitive effort influences neural choice processes in the absence of an extrinsic reward. Using functional magnetic resonance imaging in humans, we used an effort-based decision-making task in which participants were required to choose between two options for a subsequent flanker task that differed in the amount of cognitive effort. Cognitive effort was manipulated by varying the proportion of incongruent trials associated with each choice option. Choice-locked activation in the striatum was higher when participants chose voluntarily for the more effortful alternative but displayed the opposite trend on forced-choice trials. The dACC revealed a similar, yet only trend-level significant, activation pattern. Our results imply that activation levels in the striatum reflect a cost-benefit analysis, in which a balance is made between effort discounting and the intrinsic motivation to choose a cognitively challenging task. Moreover, our findings indicate that it matters whether this challenge is voluntarily chosen or externally imposed. As such, the present findings contrast with classical findings on effort discounting that found reductions in striatum activation for higher effort by finding enhancements of the same neural circuits when a cognitively challenging task is voluntarily selected and does not entail the danger of losing reward.

  18. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    OpenAIRE

    Hiroaki Kawamichi; Hiroaki Kawamichi; Hiroaki Kawamichi; Sho K Sugawara; Yuki H Hamano; Yuki H Hamano; Kai Makita; Masahiro Matsunaga; Hiroki C Tanabe; Yuichi Ogino; Shigeru Saito; Norihiro Sadato; Norihiro Sadato

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  19. Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

    OpenAIRE

    Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  20. Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism.

    Directory of Open Access Journals (Sweden)

    Zhuo Wang

    Full Text Available Exercise training is widely used for neurorehabilitation of Parkinson's disease (PD. However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions. One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [(14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula. These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum, as well as in related paralimbic regions (septum, raphe, insula. Exercise, but not lesioning, resulted

  1. Functional Reorganization of Motor and Limbic Circuits after Exercise Training in a Rat Model of Bilateral Parkinsonism

    Science.gov (United States)

    Wang, Zhuo; Myers, Kalisa G.; Guo, Yumei; Ocampo, Marco A.; Pang, Raina D.; Jakowec, Michael W.; Holschneider, Daniel P.

    2013-01-01

    Exercise training is widely used for neurorehabilitation of Parkinson’s disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases

  2. The usefulness of fractional anisotropy maps in localization of lacunar infractions in striatum, internal capsule and thalamus

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, H.K.; Lee, S.K.; Kim, D.I. [Dept. of Radiology and Research, Yonsei University Coll. of Medicine, Seoul (Korea); JHeo, J.H. [Dept. of Neurology, Yonsei University Coll. of Medicine, Seoul (Korea)

    2005-04-01

    We aimed in this study to assess the clinical usefulness of fractional anisotropy (FA) maps in the evaluation of lacunar infractions in striatum, internal capsule and thalamus. We retrospectively reviewed 28 patients (18 mean, 10 women; mean age 63 years) who had acute lacunar infraction in striatum, internal capsule and thalamus on diffusion weighted MR imaging (DWI). Fractional anisotropy (FA) maps were generated in addition to conventional T2 weigthed images (T2WI) and trace masp of DWI. Two radiologists reviewed the location of infraction was determined by FA maps. i.e. on the white band of internal capsule. Accuracy and inter-observer agreement on determination of the location of interfraction was evaluated. Accuracy of infract localization by T2WI-DWI only was varied from 72 to 91% according to the observers. Inter-observer agreement value was moderate (Kappa=0.446), when images were interpreted by T2WI-DWI only. Clinical manifestation of each lesions wre varied, but sensory motor stroke was mainly observed in thalamic lesion (50%) while pure motor hemiparesis was predominant in the case of infract involving internal capsule, corona radiata (91%) and basal ganglia (83%). The FA maps is useful in the evaluation of lacunar lesions in striatum, internal capsule and thalamus. Clinical presentation varies according to the exact location of lacunar infractions, and more accurate diagnosis can be made by FA maps as well as conventional T2-weighted image and DWI.

  3. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  4. Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

    Science.gov (United States)

    Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

    2017-11-01

    Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

  5. In situ hybridization on the change of m1 receptor mRNA in different brain areas of aged rats and the effect of Yin tonic Zhimu studied

    International Nuclear Information System (INIS)

    Hu Yaer; Xia Zongqin; Yi Ningyu

    1996-01-01

    The change of gene expression of m1 receptors in different brain areas of aged rats and the effects of water extract of the Yin tonic Zhimu and its active principle ZMS was studied. In situ hybridization using 35 S-labelled m1 and m2 probes and analysis of the autoradiographs using a computerized image-analyzer was selected. The grain density of m1 mRNA in striatum was significantly lowered in old rats as compared with young rats (decreased by 12.26 +- 3.60, P<0.01). Long-term oral administration of ZMS, the active principle of Yin tonic Zhimu but not the water extraction of Zhimu, elevated the m1 mRNA in striatum of aged rats (increased by 15.71 +- 3.27, P<0.01). Neither significant change of the grain density of m1 mRNA in old rats nor significant effect of Zhimu or ZMS was observed in cerebral cortex and hippocampus. The m1 mRNA level in striatum is decreased in aged rats and ZMS is able to elevate it

  6. Radiolabeling of codeine with 131I and its biodistribution in rats

    International Nuclear Information System (INIS)

    Enginar, H.

    2009-01-01

    Codeine which was extracted from dry capsules of the opium poppy (Papaver somniferum) was purified by HPLC (High Performance Liquid Chromatography) and characterized by NMR (Nuclear Magnetic Resonance) and IR (Infrared) spectroscopy techniques. The purified compound was labeled with 131 I and biodistribution studies were performed in rats. Radioiodinated codeine distributed uniformly in the cerebellum, m.pons, striatum and hypothalamus while the other branch of brain and Stomach, urinary bladder, and small intestine uptakes were significantly higher than other tissues. (author)

  7. Psychological Stress, Cocaine and Natural Reward Each Induce Endoplasmic Reticulum Stress Genes in Rat Brain

    OpenAIRE

    Pavlovsky, Ashly A.; Boehning, Darren; Li, Dingge; Zhang, Yafang; Fan, Xiuzhen; Green, Thomas A.

    2013-01-01

    Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors Activating Transcription Factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently it is unknown the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated. The current study examines transcriptional responses of key ER stress target genes subsequent to psychologi...

  8. Protective effect of ashwagandha (Withania somnifera against neurotoxicity induced by aluminum chloride in rats

    Directory of Open Access Journals (Sweden)

    Mohamed E Elhadidy

    2018-01-01

    Full Text Available Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminum-intoxicated rats treated daily with aluminum trichloride (AlCl3 (100 mg/kg, orally for 30 d and aluminum-intoxicated animals protected by receiving daily ashwagandha extract (200 mg/kg, orally one hour before AlCl3 administration for 30 d. Levels of lipid peroxidation, nitric oxide, reduced glutathione and tumor necrosis factor-α were measured in the cortex, hippocampus and striatum. In addition, the activities of Na+, K+, ATPase and acetylcholinesterase were determined in the three studied brain regions. Results: Aluminum increased the levels of lipid peroxidation and nitric oxide in the cortex, hippocampus and striatum and decreased the reduced glutathione level in the hippocampus and striatum. In rats protected with ashwagandha extract, non significant changes were observed in lipid peroxidation, nitric oxide and reduced glutathione. In addition, ashwagandha extracts prevented the increased activity of acetylcholinesterase and Na+, K+, ATPase induced by AlCl3 in the cortex, hippocampus and striatum. The present findings also showed that the significant increase in tumor necrosis factor-α induced by AlCl3 in the cortex and hippocampus was prevented by ashwagandha extract. Conclusions: The present results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity. In addition, ashwagandha extract could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity. The later effect could recommend the use of ashwagandha as a memory enhancer.

  9. Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

    International Nuclear Information System (INIS)

    Tomasi, D.; Fowler, J.; Tomasi, D.; Volkow, N.D.; Wang, R.L.; Telang, F.; Wang, Chang L.; Ernst, T.; Fowler, J.S.

    2009-01-01

    Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [ 11 C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.

  10. Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum.

    Science.gov (United States)

    Zhang, Jin-Tao; Ma, Shan-Shan; Li, Chiang-Shan R; Liu, Lu; Xia, Cui-Cui; Lan, Jing; Wang, Ling-Jiao; Liu, Ben; Yao, Yuan-Wei; Fang, Xiao-Yi

    2018-01-01

    Psychobehavioral intervention is an effective treatment of Internet addiction, including Internet gaming disorder (IGD). However, the neural mechanisms underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry is a common target of psychobehavioral interventions in drug addiction, and cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the study was to investigate how the VS circuitry responds to psychobehavioral interventions in IGD. In a cross-sectional study, we examined resting-state functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did not (CBI-). All participants were scanned twice with similar time interval to assess the effects of CBI. IGD subjects showed greater resting-state functional connectivity of the VS to left inferior parietal lobule (lIPL), right inferior frontal gyrus and left middle frontal gyrus, in positive association with the severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater decrease in VS-lIPL connectivity, along with amelioration in addiction severity following the intervention. These findings demonstrated that functional connectivity between VS and lIPL, each presumably mediating gaming craving and attentional bias, may be a potential biomarker of the efficacy of psychobehavioral intervention. These results also suggested that non-invasive techniques such as transcranial magnetic or direct current stimulation targeting the VS-IPL circuitry may be used in the treatment of Internet gaming disorders. © 2016 Society for the Study of Addiction.

  11. Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

    Directory of Open Access Journals (Sweden)

    John M Burkhardt

    2009-10-01

    Full Text Available Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson’s disease.

  12. S175. AMOTIVATION IS ASSOCIATED WITH SMALLER VENTRAL STRIATUM VOLUMES IN OLDER PATIENTS WITH SCHIZOPHRENIA

    Science.gov (United States)

    Caravaggio, Fernando; Fervaha, Gagan; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Nakajima, Shinichiro; Mar, Wanna; Gerretsen, Philip; Kim, Julia; Chakravarty, Mallar; Mulsant, Benoit; Pollock, Bruce; Mamo, David; Remington, Gary; Graff-Guerrero, Ariel

    2018-01-01

    Abstract Background Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long‐term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3R) blockade by antipsychotics. Methods Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D2/3R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. Results Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: β = -.38, t = -2.48, P = .01; left: β = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (β = -.43, t = -0.26, P = .03). Discussion We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D2/3R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit.

  13. Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia.

    Science.gov (United States)

    Caravaggio, Fernando; Fervaha, Gagan; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Nakajima, Shinichiro; Mar, Wanna; Gerretsen, Philip; Kim, Julia; Chakravarty, M Mallar; Mulsant, Benoit; Pollock, Bruce; Mamo, David; Remington, Gary; Graff-Guerrero, Ariel

    2018-03-01

    Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long-term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D 2/3 receptor (D 2/3 R) blockade by antipsychotics. Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D 2/3 R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: β = -.38, t = -2.48, P = .01; left: β = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (β = -.43, t = -0.26, P = .03). We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D 2/3 R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Stress-related anhedonia is associated with ventral striatum reactivity to reward and transdiagnostic psychiatric symptomatology

    Science.gov (United States)

    Corral-Frías, Nadia S.; Nikolova, Yuliya S.; Michalski, Lindsay J.; Baranger, David A.A.; Hariri, Ahmad R.; Bogdan, Ryan

    2015-01-01

    Background Early life stress (ELS) is consistently associated with increased risk for subsequent psychopathology. Individual differences in neural response to reward may confer vulnerability to stress-related psychopathology. Using data from the ongoing Duke Neurogenetics Study, the present study examined whether reward-related ventral striatum (VS) reactivity moderates the relationship between retrospectively reported ELS and anhedonic symptomatology. We further assessed whether individual differences in reward-related VS reactivity were associated with other depressive symptoms and problematic alcohol use via stress-related anhedonic symptoms and substance use-associated coping. Method Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) was collected while participants (n = 906) completed a card-guessing task, which robustly elicits VS reactivity. ELS, anhedonic symptoms, other depressive symptoms, coping behavior, and alcohol use behavior were assessed with self-report questionnaires. Linear regressions were run to examine whether VS reactivity moderated the relationship between ELS and anhedonic symptoms. Structural equation models examined whether this moderation was indirectly associated with other depression symptoms and problematic alcohol use through its association with anhedonia. Results Analyses of data from 820 participants passing quality control procedures revealed that the VS × ELS interaction was associated with anhedonic symptoms (p = 0.011). Moreover, structural equation models indirectly linked this interaction to non-anhedonic depression symptoms and problematic alcohol use through anhedonic symptoms and substance-related coping. Conclusions These findings suggest that reduced VS reactivity to reward is associated with increased risk for anhedonia in individuals exposed to ELS. Such stress-related anhedonia is further associated with other depressive symptoms and problematic alcohol use through substance-related coping

  15. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  16. Dopamine transporter gene variation modulates activation of striatum in youth with ADHD.

    Science.gov (United States)

    Bédard, Anne-Claude; Schulz, Kurt P; Cook, Edwin H; Fan, Jin; Clerkin, Suzanne M; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2010-11-15

    Polymorphisms in the 3'UTR variable number tandem repeat (VNTR) of exon 15 of the dopamine transporter gene (DAT1) have been linked to attention-deficit hyperactivity disorder (ADHD); moreover, variability in DAT1 3'UTR genotype may contribute to both heterogeneity of the ADHD phenotype and differences in response to stimulant medications. The impact of this VNTR on neuronal function in individuals with ADHD remains unclear despite evidence that the polymorphisms influence dopamine transporter expression. Thus, we used event-related functional magnetic resonance imaging to examine the impact of DAT1 3'UTR genotype on brain activation during response inhibition in unmedicated children and adolescents with ADHD. Twenty-one youth with ADHD who were homozygous for the 10-repeat (10R) allele of the DAT1 3'UTR and 12 youth who were carriers of the 9-repeat (9R) allele were scanned while they performed a Go/No-Go task. Response inhibition was modeled by contrasting activation during correct No-Go trials versus correct Go trials. Participants who were homozygous for the DAT1 3'UTR 10R allele and those who had a single 9R allele did not differ on percent of trials with successful inhibition, which was the primary measure of inhibitory control. Yet, youth with the DAT1 3'UTR 10R/10R genotype had significantly greater inhibitory control-related activation than those with one 9R allele in the left striatum, right dorsal premotor cortex, and bilaterally in the temporoparietal cortical junction. These findings provide preliminary evidence that neural activity related to inhibitory control may differ as a function of DAT1 3'UTR genotype in youth with ADHD. Copyright 2009 Elsevier Inc. All rights reserved.

  17. Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram.

    Science.gov (United States)

    Stoy, Meline; Schlagenhauf, Florian; Sterzer, Philipp; Bermpohl, Felix; Hägele, Claudia; Suchotzki, Kristina; Schmack, Katharina; Wrase, Jana; Ricken, Roland; Knutson, Brian; Adli, Mazda; Bauer, Michael; Heinz, Andreas; Ströhle, Andreas

    2012-05-01

    Major Depressive Disorder (MDD) involves deficits in the reward system. While neuroimaging studies have focused on affective stimulus processing, few investigations have directly addressed deficits in the anticipation of incentives. We examined neural responses during gain and loss anticipation in patients with MDD before and after treatment with a selective serotonin reuptake inhibitor (SSRI). Fifteen adults with MDD and 15 healthy participants, matched for age, verbal IQ and smoking habits, were investigated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay task. Patients were scanned drug-free and after 6 weeks of open-label treatment with escitalopram; controls were scanned twice at corresponding time points. We compared the blood oxygenation level dependent (BOLD) response during the anticipation of gain and loss with a neutral condition. A repeated measures ANOVA was calculated to identify effects of group (MDD vs. controls), time (first vs. second scan) and group-by-time interaction. Severity of depression was measured with the Hamilton Rating Scale of Depression and the Beck Depression Inventory. MDD patients showed significantly less ventral striatal activation during anticipation of gain and loss compared with controls before, but not after, treatment. There was a significant group-by-time interaction during anticipation of loss in the left ventral striatum due to a signal increase in patients after treatment. Ventral striatal hyporesponsiveness was associated with the severity of depression and in particular anhedonic symptoms. These findings suggest that MDD patients show ventral striatal hyporesponsiveness during incentive cue processing, which normalizes after successful treatment.

  18. Methanol extract of Nigella sativa seed induces changes in the levels of neurotransmitter amino acids in male rat brain regions.

    Science.gov (United States)

    El-Naggar, Tarek; Carretero, María Emilia; Arce, Carmen; Gómez-Serranillos, María Pilar

    2017-12-01

    Nigella sativa L. (Ranunculaceae) (NS) has been used for medicinal and culinary purposes. Different parts of the plant are used to treat many disorders. This study investigates the effects of NS methanol extract on brain neurotransmitter amino acid levels. We measured the changes in aspartate, glutamate, glycine and γ-aminobutyric acid in five brain regions of male Wistar rats after methanol extract treatment. Animals were injected intraperitoneally with saline solution (controls) or NS methanol extract (equivalent of 2.5 g/kg body weight) and sacrificed 1 h later or after administering 1 daily dose for 8 days. The neurotransmitters were measured in the hypothalamus, cortex, striatum, hippocampus and thalamus by HPLC. Results showed significant changes in amino acids compared to basal values. Glutamate increased significantly (16-36%) in the regions analyzed except the striatum. Aspartate in the hypothalamus (50 and 76%) and glycine in hippocampus (32 and 25%), thalamus (66 and 29%) and striatum (75 and 48%) also increased with the two treatment intervals. γ-Aminobutyric acid significantly increased in the hippocampus (38 and 32%) and thalamus (22 and 40%) but decreased in the cortex and hypothalamus although in striatum only after eight days of treatment (24%). Our results suggest that injected methanol extract modifies amino acid levels in the rat brain regions. These results could be of interest since some neurodegenerative diseases are related to amino acid level imbalances in the central nervous system, suggesting the prospect for therapeutic use of NS against these disorders.

  19. Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Gulati, A.; Bhargava, H.N.

    1990-01-01

    The binding of [ 3 H] DAMGO, a highly selective ligand for μ-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [ 3 H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B max value) and apparent dissociation constant (K d value) of [ 3 H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B max value of [ 3 H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K d values in the two strains did not differ. On the other hand, the B max value of [ 3 H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K d values in the two strains were similar

  20. Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-01-01

    The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

  1. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

    2010-09-01

    Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex.

    Science.gov (United States)

    Rezin, Gislaine T; Scaini, Giselli; Gonçalves, Cinara L; Ferreira, Gabriela K; Cardoso, Mariane R; Ferreira, Andréa G K; Cunha, Maira J; Schmitz, Felipe; Varela, Roger B; Quevedo, João; Wyse, Angela T S; Streck, Emilio L

    2014-01-01

    Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability.

  3. Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

    Directory of Open Access Journals (Sweden)

    Gislaine T. Rezin

    2014-05-01

    Full Text Available Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally or polysorbate 80 (control group. Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability.

  4. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

    Science.gov (United States)

    Meng, Chun; Brandl, Felix; Tahmasian, Masoud; Shao, Junming; Manoliu, Andrei; Scherr, Martin; Schwerthöffer, Dirk; Bäuml, Josef; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

    2014-02-01

    In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter

  6. Dopamine receptor gene expression by enkephalin neurons in rat forebrain

    International Nuclear Information System (INIS)

    Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B.

    1990-01-01

    In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons

  7. Dopamine receptor gene expression by enkephalin neurons in rat forebrain

    Energy Technology Data Exchange (ETDEWEB)

    Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B. (Universite de Bordeaux II (France))

    1990-01-01

    In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons.

  8. Inability to acquire spatial information and deploy spatial search strategies in mice with lesions in dorsomedial striatum.

    Science.gov (United States)

    Pooters, Tine; Gantois, Ilse; Vermaercke, Ben; D'Hooge, Rudi

    2016-02-01

    Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

    Directory of Open Access Journals (Sweden)

    Atsushi Tamura

    Full Text Available The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+ signaling. To characterize Ca(2+ signaling in striatal cells, spontaneous cytoplasmic Ca(2+ transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP in the astrocytes. In both the GFP-negative cells (putative-neurons and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+ transients (referred to as slow Ca(2+ oscillations, which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+ oscillation. Depletion of the intracellular Ca(2+ store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+ oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+ oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+ oscillation in both putative-neurons and astrocytes. The slow Ca(2+ oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+ oscillation may involve in the neuron-glia interaction in the striatum.

  10. Study on microstructure of corpus striatum in patients with idiopathic rapid eye movement sleep behavior disorder using magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Ya-meng ZHANG

    2017-07-01

    Full Text Available Objective To investigate the structure of corpus striatum and the integrity of white matter fiber in patients with Parkinson's disease (PD and idiopathic rapid eye movement sleep behavior disorder (iRBD.  Methods Twelve patients with iRBD, 12 patients with PD and 10 healthy subjects that were well matched in gender, age and education were enrolled in this study. Head MRI examination was performed to all subjects to observe the changes of corpus striatum structure (the gray matter volume and the integrity of white matter fiber [fractional anisotropy (FA] by combining voxel?based morphometry (VBM and diffusion tensor imaging (DTI.  Results Compared with healthy subjects, the gray matter volume of left caudate nucleus was significantly decreased (P < 0.005, and FA values of left caudate nucleus (P < 0.005, right caudate nucleus (P < 0.001 and right putamen (P < 0.05 were all significantly reduced in iRBD patients; FA value of right putamen was significantly decreased in PD patients (P < 0.05. Compared with PD patients, the gray matter volume of left caudate nucleus of iRBD patients was significantly reduced (P < 0.001, FA values of left caudate nucleus (P < 0.01 and right caudate nucleus (P < 0.005 of iRBD patients were significantly reduced.  Conclusions There is atrophy of gray matter volume and extensive white matter fiber impairment in corpus striatum of patients with iRBD, and the white matter fiber impairment was similar to PD, which provides an anatomical evidence for iRBD being presymptom of PD. DOI: 10.3969/j.issn.1672-6731.2017.05.008

  11. Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum.

    Science.gov (United States)

    Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

    2018-04-01

    The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

  12. Reinforcement learning signals in the human striatum distinguish learners from nonlearners during reward-based decision making.

    Science.gov (United States)

    Schönberg, Tom; Daw, Nathaniel D; Joel, Daphna; O'Doherty, John P

    2007-11-21

    The computational framework of reinforcement learning has been used to forward our understanding of the neural mechanisms underlying reward learning and decision-making behavior. It is known that humans vary widely in their performance in decision-making tasks. Here, we used a simple four-armed bandit task in which subjects are almost evenly split into two groups on the basis of their performance: those who do learn to favor choice of the optimal action and those who do not. Using models of reinforcement learning we sought to determine the neural basis of these intrinsic differences in performance by scanning both groups with functional magnetic resonance imaging. We scanned 29 subjects while they performed the reward-based decision-making task. Our results suggest that these two groups differ markedly in the degree to which reinforcement learning signals in the striatum are engaged during task performance. While the learners showed robust prediction error signals in both the ventral and dorsal striatum during learning, the nonlearner group showed a marked absence of such signals. Moreover, the magnitude of prediction error signals in a region of dorsal striatum correlated significantly with a measure of behavioral performance across all subjects. These findings support a crucial role of prediction error signals, likely originating from dopaminergic midbrain neurons, in enabling learning of action selection preferences on the basis of obtained rewards. Thus, spontaneously observed individual differences in decision making performance demonstrate the suggested dependence of this type of learning on the functional integrity of the dopaminergic striatal system in humans.

  13. [Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

    Science.gov (United States)

    Leontovich, T A; Zvegintseva, E G

    1985-10-01

    Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.

  14. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

    DEFF Research Database (Denmark)

    Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

    2017-01-01

    The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...... diameters and conduction distance are monkey and, by extrapolation,

  15. Proteomic Analysis of the Effect of Korean Red Ginseng in the Striatum of a Parkinson?s Disease Mouse Model

    OpenAIRE

    Kim, Dongsoo; Jeon, Hyongjun; Ryu, Sun; Koo, Sungtae; Ha, Ki-Tae; Kim, Seungtae

    2016-01-01

    Recent studies have shown that Korean Red Ginseng (KRG) suppresses dopaminergic neuronal death in the brain of a Parkinson's disease (PD) mouse model, but the mechanism is still elusive. Using a 2-dimensional electrophoresis technique, we investigated whether KRG can restore the changes in protein expressions in the striatum (ST) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Male C57BL/6 mice (9 weeks old) were injected with 20 mg/kg MPTP intraperitoneally four times a...

  16. Binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine (AV-133) to the vesicular monoamine transporter type 2 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, H.-H. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Lin, K.-J. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Department of Nuclear Medicine, Chang Gung University and Memorial Hospital, Taoyuan, Taiwan (China); Juang, J.-H. [Division of Endocrinology and Metabolism, Chung Gung University and Chung Gung Memorial Hospital, Taoyuan, Taiwan (China); Skovronsky, Daniel M. [Avid Radiopharmaceuticals, Philadelphia, PA (United States); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Yen, T.-C. [Department of Nuclear Medicine, Chang Gung University and Memorial Hospital, Taoyuan, Taiwan (China); Wey, S.-P. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Kung, M.-P. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States)], E-mail: kungmp@sunmac.spect.upenn.edu

    2010-05-15

    The vesicular monoamine transporter type 2 (VMAT2) is highly expressed in pancreatic {beta}-cells and thus has been proposed to be a potential target for measuring {beta}-cell mass (BCM) by molecular imaging. C-11- and F-18-labeled tetrabenazine derivatives targeting VMAT2 have shown some promising results as potential biomarkers for BCM. In the present study, we examined the binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine ([{sup 18}F]AV-133), a potential PET tracer for BCM imaging, in rat pancreas and rat brain. Methods: Pancreatic exocrine cells and pancreatic islet cells were isolated and purified from Sprague-Dawley rats. Membrane homogenates, prepared from both pancreatic exocrine and islet cells as well as from brain striatum and hypothalamus regions, were used for in vitro binding studies. In vitro and ex vivo autoradiography studies with [{sup 18}F]AV-133 were performed on rat brain and rat pancreas sections. Immunohistochemistry studies were performed to confirm the distribution of VMAT2 on islet {beta}-cells. Results: Excellent binding affinities of [{sup 18}F]AV-133 were observed in rat striatum and hypothalamus homogenates with K{sub d} values of 0.19 and 0.25 nM, respectively. In contrast to single-site binding observed in rat striatum homogenates, rat islet cell homogenates showed two saturable binding sites (site A: K{sub d}=6.76 nM, B{sub max}=60 fmol/mg protein; site B: K{sub d}=241 nM, B{sub max}=1500 fmol/mg protein). Rat exocrine pancreas homogenates showed only a single low-affinity binding site (K{sub d}=209 nM), which was similar to site B in islet cells. In vitro autoradiography of [{sup 18}F]AV-133 using frozen sections of rat pancreas showed specific labeling of islets, as evidenced by co-localization with anti-insulin antibody. Ex vivo VMAT2 pancreatic autoradiography in the rat, however, was not successful, in contrast to the excellent ex vivo autoradiography of VMAT2 binding sites in the brain. In vivo/ex vivo islet

  17. 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...

  18. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  19. Reward prediction error signal enhanced by striatum-amygdala interaction explains the acceleration of probabilistic reward learning by emotion.

    Science.gov (United States)

    Watanabe, Noriya; Sakagami, Masamichi; Haruno, Masahiko

    2013-03-06

    Learning does not only depend on rationality, because real-life learning cannot be isolated from emotion or social factors. Therefore, it is intriguing to determine how emotion changes learning, and to identify which neural substrates underlie this interaction. Here, we show that the task-independent presentation of an emotional face before a reward-predicting cue increases the speed of cue-reward association learning in human subjects compared with trials in which a neutral face is presented. This phenomenon was attributable to an increase in the learning rate, which regulates reward prediction errors. Parallel to these behavioral findings, functional magnetic resonance imaging demonstrated that presentation of an emotional face enhanced reward prediction error (RPE) signal in the ventral striatum. In addition, we also found a functional link between this enhanced RPE signal and increased activity in the amygdala following presentation of an emotional face. Thus, this study revealed an acceleration of cue-reward association learning by emotion, and underscored a role of striatum-amygdala interactions in the modulation of the reward prediction errors by emotion.

  20. No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.

    Science.gov (United States)

    Müller, Kathrin U; Gan, Gabriela; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Schumann, Gunter; Smolka, Michael N

    2015-05-01

    Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit. © 2014 Society for the Study of Addiction.

  1. MicroRNA-124 slows down the progression of Huntington′s disease by promoting neurogenesis in the striatum

    Directory of Open Access Journals (Sweden)

    Tian Liu

    2015-01-01

    Full Text Available MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington′s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington′s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington′s disease transgenic mouse in the rotarod test. 5-Bromo-2′-deoxyuridine (BrdU staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington′s disease possibly through its important role in neuronal differentiation and survival.

  2. Mechanisms of Neuroplasticity and Ethanol’s Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis

    Science.gov (United States)

    Lovinger, David M.; Kash, Thomas L.

    2015-01-01

    Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction. Two brain regions subject to alcohol’s effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol’s actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder. PMID:26259092

  3. Reduced expression of Nogo-A leads to motivational deficits in rats

    Directory of Open Access Journals (Sweden)

    Thomas eEnkel

    2014-01-01

    Full Text Available Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased prepulse inhibition and behavioral inflexibility. In the current study we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex, dorsal striatum and nucleus accumbens. Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A rats exhibited lower break points and tended to have lower ‘highest completed ratios’. Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the prefrontal cortex we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dorsal striatum and the nucleus accumbens. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

  4. Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

    Directory of Open Access Journals (Sweden)

    Malihe Nakhaeifard

    2016-02-01

    Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

  5. DISTRIBUTION OF MONOAMINES AND THEIR METABOLITES IN BOTH SIDES OF THE RAT BRAIN AND ITS RELATION WITH FUNCTIONAL MOTOR ASYMMETRY

    OpenAIRE

    E.D. Morenkov; V.S. Kudrin

    2013-01-01

    The purpose of this neurochemical study was to quantitatively determine the regional distribution of monoamines (DA, 5HT, and NE) and their metabolites (DOPAC, HVA, and 5HIAA) in paired brain structures (the frontomedial cortex, hypothalamus, amygdala, hippocampus, striatum, and brainstem tegmentum) of the rat by performing HPLC/ED assays. Further, we aimed to relate these distributions to neuronal mechanisms of lateralized motor behavior. We found differences in monoamine levels and their...

  6. Exploration of central dopamine transporter and D2 receptor in morphine abstinent rats

    International Nuclear Information System (INIS)

    Lin Yansong; Wang Bocheng; Wang Shizhen; Ding Shiyu; Chen Zhengping; Zhang Manda

    2006-01-01

    The experiment was designed to investigate the variation of DAT and D2 receptor in morphine administered and 1,2,3 day abstinent rats. Morphine exposure was induced by repeated morphine (i.p.) treatment for 8 days. Conditioned place preference test was conducted to evaluate the drug seeking behaviour and morphine dependence of rats with morphine exposure. Biodistribution of the imaging agents 125 I-β-CIT and 125 I-IBZM was used to evaluate the central DAT and D2 receptor during morphine exposure and 1,2,3 day's abstinence. Results reveal the following facts. (1) The morphine abstinent rats showed diarrhea and body-shake 1 day after morphine withdrawal. (2) For morphine group, 125 I-β-CIT %ID/g in ST and NAC was higher than that of the 1,2,3 day's abstinent rats and control (P 0.05). (3) 125 I-IBZM %ID/g in ST, NAC and HIP in morphine rats were lower than those of the abstinent and control rats (P 125 I-IBZM %ID/g in ST and NAC gradually increased with the abstinent days. While in ST the %ID/g among the abstinent rats was all lower than that of the control rats, in NAC the %ID/g was still lower in 1 day's abstinent rats (P 0.05), indicating the reduction of hyper-activated DAT and the increase of down-regulatory D2 receptor induced by morphine during morphine withdrawal. Our results confirmed that the dopamine system, especially DAT and D2 receptor in mesolimbic and meso-striatum pathway, has been implicated in morphine treatment. The rewarding properties of morphine and the somatic expression of morphine abstinence were related to changes in mesolimbic and meso-striatum dopaminergic activity. (authors)

  7. Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

    Science.gov (United States)

    Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

    2009-01-01

    The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

  8. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    Science.gov (United States)

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

  9. Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

    Science.gov (United States)

    Song, Qifan; Deng, Yu; Yang, Xinxin; Bai, Ying; Xu, Bin; Liu, Wei; Zheng, Wenxue; Wang, Can; Zhang, Meng; Xu, Zhaofa

    2016-12-01

    Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl 2 group, 25 mg/kg MnCl 2 group, and 50 mg/kg MnCl 2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl 2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

  10. [Alternation of proteins in brain of Parkinson's disease model rats after the transplantation of TH-NTN gene modified bone marrow mesenchymal stem cells].

    Science.gov (United States)

    Huang, Yue; Chang, Cheng; Zhang, Jie-wen; Gao, Xiao-qun

    2012-09-04

    To explore the effects of tyrosine hydroxylase-neurturin (TH-NTN) gene modified bone marrow mesenchymal stem cell (BMSC) transplantation in Parkinson's disease (PD) model rats and the alternations of correlated proteins. The PD rat model was established by the 2-point injection of 6-hydroxydopamine (6-OHDA) into unilateral (right) striatum. Successful modeling rats were separated into PD, BMSC and TH-NTN-BMSC groups. BMSC and TH-NTN-BMSC groups were transplanted into BMSCs and TH-NTN gene modified BMSC cells separately into right striatum. After transplantation, ethology detection in all groups was made with an intraperitoneal injection of apomorphine (APO). Dopamine (DA) and Dihydroxyphenylacetic Acid (DOPAC) in striatum were detected by high performance liquid electrochemical analysis. TH and NTN proteins in right striatum were also analyzed by immunohistochemistry and Western blot. Finally the density of dopamine receptors in post synaptic density of dopaminergic synapses of corpus striatum were compared between each group by post-embedding immunogold electron microscopy. After an injection of APO, rotation frequency decreased in TH-NTN-BMSC group, i.e. (5.7 ± 1.3) circles/min versus (10.8 ± 2.2), (9.9 ± 1.2) circles/min in PD and BMSC groups (P TH-NTN-BMSC group versus (923 ± 132)/µm(2) in PD and (860 ± 116)/µm(2) in BMSC groups was also found. The combined therapy of TH and NTN genes increases the synthesis of DA and also protects the dopaminergic neurons to achieve double therapeutic effects. It may provide potential innovations of PD genetic therapy.

  11. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    Science.gov (United States)

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

  12. Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

    Science.gov (United States)

    Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

    2007-02-09

    Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward

  13. 5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.

    Science.gov (United States)

    Ya, Bai-Liu; Li, Hong-Fang; Wang, Hai-Ying; Wu, Fei; Xin, Qing; Cheng, Hong-Ju; Li, Wen-Juan; Lin, Na; Ba, Zai-Hua; Zhang, Ru-Juan; Liu, Qian; Li, Ya-Nan; Bai, Bo; Ge, Feng

    2017-01-01

    Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that

  14. More consistently altered connectivity patterns for cerebellum and medial temporal lobes than for amygdala and striatum in schizophrenia

    Directory of Open Access Journals (Sweden)

    Henning ePeters

    2016-02-01

    Full Text Available Background: Brain architecture can be divided into a cortico-thalamic system and modulatory ‘subcortical-cerebellar’ systems containing key structures such as striatum, medial temporal lobes (MTLs, amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems’ connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems’ connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI. Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems’ activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs (i.e., striatum, MTL, amygdala, cerebellum. Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices (i.e. connectivity between NW and ROIs (allROIs-NW, separateROI-NW, only NWs (NWs-NWs, and only ROIs (allROIs-allROIs as main outcome measures, which were classified by support-vector-machine-based leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56% and 74%, respectively. Considering separate

  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. Oxidative stress in a model of toxic demyelination in rat brain: the effect of piracetam and vinpocetine.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Khadrawy, Yasser A; Salem, Neveen A; Sleem, Amany A

    2011-06-01

    We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

  17. Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

    Directory of Open Access Journals (Sweden)

    Pierre eTrifilieff

    2013-06-01

    Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

  18. Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum

    DEFF Research Database (Denmark)

    Deserno, Lorenz; Beck, Anne; Huys, Quentin J. M.

    2015-01-01

    Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug......-related stimuli towards drug-related stimuli. Such ‘hijacked’ dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs......) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[18F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation...

  19. The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Jacqueline H Byrne

    Full Text Available BACKGROUND: Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. METHODS: Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT and the 5 choice continuous performance task (5C-CPT and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. RESULTS: AVD-deficient rats were deficient in vitamin D3 (<10 nM and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. CONCLUSIONS: AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

  20. The Role of the Neuropeptide Somatostatin on Methamphetamine and Glutamate-Induced Neurotoxicity in the Striatum of Mice

    Science.gov (United States)

    Afanador, Lauriaselle; Mexhitaj, Ina; Diaz, Carolyn; Ordonez, Dalila; Baker, Lisa; Angulo, Jesus A.

    2014-01-01

    A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30 mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms. PMID:23524190

  1. The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

    Science.gov (United States)

    Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

    2007-08-15

    Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

  2. Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

    Science.gov (United States)

    Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

    2014-05-01

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

  3. The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

    Science.gov (United States)

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-01-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

  4. Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

    Science.gov (United States)

    Choi, Chi-Bong; Kim, Sang-Young; Lee, Sung-Ho; Jahng, Geon-Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung-Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo-Suk

    2011-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.

    Science.gov (United States)

    Pfabigan, Daniela M; Seidel, Eva-Maria; Sladky, Ronald; Hahn, Andreas; Paul, Katharina; Grahl, Arvina; Küblböck, Martin; Kraus, Christoph; Hummer, Allan; Kranz, Georg S; Windischberger, Christian; Lanzenberger, Rupert; Lamm, Claus

    2014-08-01

    The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. Copyright © 2014. Published by Elsevier Inc.

  6. Different involvement of medial prefrontal cortex and dorso-lateral striatum in automatic and controlled processing of a future conditioned stimulus.

    Science.gov (United States)

    Pérez-Díaz, Francisco; Díaz, Estrella; Sánchez, Natividad; Vargas, Juan Pedro; Pearce, John M; López, Juan Carlos

    2017-01-01

    Recent studies support the idea that stimulus processing in latent inhibition can vary during the course of preexposure. Controlled attentional mechanisms are said to be important in the early stages of preexposure, while in later stages animals adopt automatic processing of the stimulus to be used for conditioning. Given this distinction, it is possible that both types of processing are governed by different neural systems, affecting differentially the retrieval of information about the stimulus. In the present study we tested if a lesion to the dorso-lateral striatum or to the medial prefrontal cortex has a selective effect on exposure to the future conditioned stimulus (CS). With this aim, animals received different amounts of exposure to the future CS. The results showed that a lesion to the medial prefrontal cortex enhanced latent inhibition in animals receiving limited preexposure to the CS, but had no effect in animals receiving extended preexposure to the CS. The lesion of the dorso-lateral striatum produced a decrease in latent inhibition, but only in animals with an extended exposure to the future conditioned stimulus. These results suggest that the dorsal striatum and medial prefrontal cortex play essential roles in controlled and automatic processes. Automatic attentional processes appear to be impaired by a lesion to the dorso-lateral striatum and facilitated by a lesion to the prefrontal cortex.

  7. Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.

    Directory of Open Access Journals (Sweden)

    Yonghua Cui

    Full Text Available The exposures to extremely low frequency magnetic field (ELF-MF in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.

  8. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

    Directory of Open Access Journals (Sweden)

    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  9. Exploration of central dopamine D2 receptors by autoradiography, pathology and functional behaviour observation in rat model with experimental parkinsonism

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    1996-01-01

    The rat model with experimental parkinsonism mimic the course of human parkinsonism were made by cerebral-stereotaxic techniques. 125 I-IBZM was used to evaluate the D 2 receptors distribution by autoradiographic analysis of coronal brain section. In 6 parkinsonism model rats, on the lesioned side the striatum/frontal cortex ratio was 5.32 +- 0.37, it was significantly (P 125 I-IBZM as the ligand of D 2 receptor can well reflect the distribution and changes of D 2 receptors, and also as the theoretical basis for the clinical imaging diagnosis

  10. High affinity binding of [3H]cocaine to rat liver microsomes

    International Nuclear Information System (INIS)

    El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

    1988-01-01

    ] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  11. Sequential changes in ischemic edema following transient focal cerebral ischemia in rats; Magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Nagahiro, Shinji; Goto, Satoshi; Kogo, Kasei; Sumi, Minako; Takahashi, Mutsumasa; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    1994-07-01

    Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T[sub 2]-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T[sub 2] high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T[sub 2] high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema. (author).

  12. Overexpression of parkin in rat nigrostriatal dopamine system protects against methamphetamine neurotoxicity

    Science.gov (United States)

    Liu, Bin; Traini, Roberta; Killinger, Bryan; Schneider, Bernard; Moszczynska, Anna

    2013-01-01

    Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previously detected a deficit in parkin after binge METH in rat striatal synaptosomes. Parkin is an ubiquitin-protein E3 ligase capable of protecting dopamine neurons from diverse cellular insults. Whether the deficit in parkin mediates the toxicity of METH and whether parkin can protect from toxicity of the drug is unknown. The present study investigated whether overexpression of parkin attenuates degeneration of striatal dopaminergic terminals exposed to binge METH. Parkin overexpression in rat nigrostriatal dopamine system was achieved by microinjection of adeno-associated viral transfer vector 2/6 encoding rat parkin (AAV2/6-parkin) into the substantia nigra pars compacta. The microinjections of AAV2/6-parkin dose-dependently increased parkin levels in both the substantia nigra pars compacta and striatum. The levels of dopamine synthesizing enzyme, tyrosine hydroxylase, remained at the control levels; therefore, tyrosine hydroxylase immunoreactivity was used as an index of dopaminergic terminal integrity. In METH-exposed rats, the increase in parkin levels attenuated METH-induced decreases in striatal tyrosine hydroxylase immunoreactivity in a dose-dependent manner, indicating that parkin can protect striatal dopaminergic terminals against METH neurotoxicity. PMID:23313192

  13. Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

    Science.gov (United States)

    Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

    2014-10-01

    Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. Copyright © 2014. Published by Elsevier Inc.

  14. The putative cocaine receptor in striatum is a glycoprotein with thiol function

    International Nuclear Information System (INIS)

    Cao, C.J.; Young, M.M.; Wang, J.B.; Mahran, L.; Eldefrawi, M.E.

    1990-01-01

    Dopamine transporters of bovine and rat striata are identified by their specific [ 3 H] cocaine binding and cocaine-sensitive [ 3 H] dopamine ([ 3 H]DA) uptake. Both binding and uptake functions of bovine striatal transporters were potentiated by lectins. Concanavalin A (Con A) increased the velocity but did not change the affinity of the transporter for DA. On the other hand, ConA increased its affinity for cocaine without changing the number of binding sites. The data suggest that the DA transporter is a glycoprotein. Inorganic and organic mercury reagents inhibited both [ 3 H] cocaine binding, though they were all more potent inhibitors of the former. N-ethylmaleimide inhibited [ 3 H]DA uptake totally but [ 3 H]cocaine binding only partially. Also, N-pyrenemaleimide had different effects on uptake and binding, inhibiting uptake and potentiating binding. [ 3 H]DA uptake was not affected by mercaptoethanol up to 100 mM whereas [ 3 H]cocaine binding was inhibited by concentration above 10 mM. On the other hand, both uptake and binding were fairly sensitive to dimercaprol ( 10 mM). Loss of activity after treatment with the dithio reagents may be a result of reduction of a disulfide bond, which may affect the transporter conformation

  15. In vivo characteristics of IBZM in rat brains, an agent for quantitative SPECT imaging of D2 dopamine receptors. A basis for semiquantitative measurement of the receptor density using equilibrium analysis

    International Nuclear Information System (INIS)

    Toyama, Hiroshi; Maeda, Hisato; Takeuchi, Akira; Koga, Sukehiko; Matsumura, Kaname; Nakashima, Hiromichi; Ichise, Masanori; Kurami, Miki; Nakagawa, Tsuyoshi.

    1994-01-01

    To establish a basis for semiquantitative SPECT measurements of the D 2 dopamine receptor density using equilibrium analysis, we evaluated in vivo kinetic properties of 125 I-IBZM in rat brains. We measured percent uptakes (% dose/g) of 125 I-IBZM in the striatum, frontal cortex, and cerebellum. We made these regional measurements at 15, 30, 45, 60, 90, and 120 minutes after injection, respectively. The specific striatal uptake, which is the uptake difference between striatum and frontal cortex or cerebellum, showed a transient equilibrium phase at 60 min. Theoretically, with these 'reversible' D 2 receptor binding ligands, the tracer-uptake ratio of the striatum-to-frontal cortex or cerebellum during the equilibrium phase provides an estimate of binding potential (Bound/Free=B max /K d ). Our experiment showed that these ratio increased with time after bolus injection of the tracer. Striatum to frontal cortex or cerebellum ratios which were calculated with pooled data (n=12) at 60 minutes in equilibrium phase showed nearly constant values (C.V.=12.3% and 13.5%, respectively). Although measuring the striatum to frontal cortex or cerebellum ratios near equilibrium phase by bolus injection of the tracer which are widely used in human SPECT study could not exactly signify the binding potential, those ratios at fixed time after injection would be reliable for semiquantitative index. (author)

  16. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    Science.gov (United States)

    Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

    2015-01-01

    AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

  17. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    International Nuclear Information System (INIS)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N.

    1991-01-01

    The binding of 3 H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. 3 H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of 3 H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B max value) and apparent dissociation constant (K d value) values of 3 H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B max value of 3 H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K d values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with 3 H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats

  18. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  19. The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia.

    Science.gov (United States)

    Réus, Gislaine Z; Becker, Indianara R T; Scaini, Giselli; Petronilho, Fabricia; Oses, Jean P; Kaddurah-Daouk, Rima; Ceretta, Luciane B; Zugno, Alexandra I; Dal-Pizzol, Felipe; Quevedo, João; Barichello, Tatiana

    2018-02-02

    Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes. In addition, the IDO inhibitor prevented lipid peroxidation, and decreased the levels of protein carbonyl in the prefrontal cortex (PFC), hippocampus and striatum. It also increased the activity of superoxide dismutase (SOD) in the hippocampus, as well as increasing the levels of catalase activity in the PFC and hippocampus. The TDO inhibitor prevented lipid damage in the striatum and reduced the levels of protein carbonyl in the hippocampus and striatum. Also, the TDO inhibitor increased the levels of SOD activity in the striatum and CAT activity in the hippocampus of ketamine-induced pro-oxidant effects. Lipid damage was not reversed by the KMO inhibitor. The KMO inhibitor increased the levels of SOD activity in the hippocampus, and reduced the levels of protein carbonyl while elevating the levels of CAT activity in the striatum of rats that had been injected with ketamine. Our findings revealed that the KP pathway could be a potential mechanism by which a schizophrenia animal model induced by ketamine could cause interference by producing behavioral disturbance and inducing oxidative stress in the brain, suggesting that the inhibition of the KP pathway could be a potential target in treating schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Antibiotic treatment attenuates behavioral and neurochemical changes induced by exposure of rats to group a streptococcal antigen.

    Directory of Open Access Journals (Sweden)

    Dafna Lotan

    Full Text Available Post-streptococcal A (GAS sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter's possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.

  1. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

  2. Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jonathan Wills

    2011-03-01

    Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

  3. Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances.

    Science.gov (United States)

    Avinun, Reut; Nevo, Adam; Knodt, Annchen R; Elliott, Maxwell L; Radtke, Spenser R; Brigidi, Bartholomew D; Hariri, Ahmad R

    2017-10-04

    Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression. SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity

  4. Cocaine self-administration differentially affects allosteric A2A-D2 receptor-receptor interactions in the striatum. Relevance for cocaine use disorder.

    Science.gov (United States)

    Pintsuk, Julia; Borroto-Escuela, Dasiel O; Pomierny, Bartosz; Wydra, Karolina; Zaniewska, Magdalena; Filip, Malgorzata; Fuxe, Kjell

    2016-05-01

    In the current study behavioral and biochemical experiments were performed to study changes in the allosteric A2AR-D2R interactions in the ventral and dorsal striatum after cocaine self-administration versus corresponding yoked saline control. By using ex vivo [(3)H]-raclopride/quinpirole competition experiments, the effects of the A2AR agonist CGS 21680 (100 nM) on the KiH and KiL values of the D2-like receptor (D2-likeR) were determined. One major result was a significant reduction in the D2-likeR agonist high affinity state observed with CGS 21680 after cocaine self-administration in the ventral striatum compared with the yoked saline group. The results therefore support the hypothesis that A2AR agonists can at least in part counteract the motivational actions of cocaine. This action is mediated via the D2-likeR by targeting the A2AR protomer of A2AR-D2-like R heteroreceptor complexes in the ventral striatum, which leads to the reduction of D2-likeR protomer recognition through the allosteric receptor-receptor interaction. In contrast, in the dorsal striatum the CGS 21680-induced antagonistic modulation in the D2-likeR agonist high affinity state was abolished after cocaine self-administration versus the yoked saline group probably due to a local dysfunction/disruption of the A2AR-D2-like R heteroreceptor complexes. Such a change in the dorsal striatum in cocaine self-administration can contribute to the development of either locomotor sensitization, habit-forming learning and/or the compulsive drug seeking by enhanced D2-likeR protomer signaling. Potential differences in the composition and stoichiometry of the A2AR-D2R heteroreceptor complexes, including differential recruitment of sigma 1 receptor, in the ventral and dorsal striatum may explain the differential regional changes observed in the A2A-D2-likeR interactions after cocaine self-administration. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

    Science.gov (United States)

    Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Kim, Kyoung-Shim; Han, Pyung-Lim

    2014-11-07

    Behavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices. Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes. Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such

  6. Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

    Science.gov (United States)

    Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

    2013-10-10

    Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (pmotor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Motor activity changes induced by sub-encephalopathic lead exposure during different developmental phases in rats

    International Nuclear Information System (INIS)

    Van Rooyen, J.M.; Offermeier, J.; Brand, L.; Botha, F.; Rossouw, J.; Lategan, A.J.; Botes, M.S.

    1988-01-01

    Two groups of rats were exposed to lead (0,2% lead acetate in drinking water) for periods of 21 days during different developmental phases. Lead exposure was initiated on day 1 and day 22 after birth, for rats in groups 1 and 2, respectively. Measurements of locomotor activity (LA) and [ 3 H]spiperone binding assays were performed on day 50 after birth. Lead exposure resulted in the potentiation of the LA effects of 5 mg/kg apomorphine without altering the LA effects of 50 mg/kg piribedil in group 1. Lead exposure resulted in an attenuation of the LA effects of apomorphine and piribedil in group 2. Lead exposure did not alter the K D and B max values of [ 3 H]spiperone in membranes prepared from the rat striatum or nucleus accumbens

  8. Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

    International Nuclear Information System (INIS)

    Inaji, Motoki; Okauchi, Takashi; Nagai, Yuji; Nojima, Kumie; Suhara, Tetsuya

    2004-01-01

    The present study was designed to make a new Parkinson disease model using carbon ion beam. In this year, we irradiated right middle forebrain bundle of adult rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars which was developed in this year. In 4 weeks after the irradiation, we performed methamphetamine induced rotation test and the autoradiography measurement on dopamine transporter using [ 11 C]PE2I to assess degeneration of dopaminergic neurons in caudate putamen (Cpu). As a result, ipsilateral rotation was observed and the distributions of dopamine transporter in the striatum decreased significantly. These results are similar to those of 6-OHDA lesioned rats, and indicate validity of this model. (author)

  9. Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

    Science.gov (United States)

    Robinson, S E; Mo, Q; Maher, J R; Wallace, M J; Kunko, P M

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

  10. Motor activity changes induced by sub-encephalopathic lead exposure during different developmental phases in rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rooyen, J M; Offermeier, J; Brand, L; Botha, F; Rossouw, J; Lategan, A J; Botes, M S

    1988-05-01

    Two groups of rats were exposed to lead (0,2% lead acetate in drinking water) for periods of 21 days during different developmental phases. Lead exposure was initiated on day 1 and day 22 after birth, for rats in groups 1 and 2, respectively. Measurements of locomotor activity (LA) and (/sup 3/H)spiperone binding assays were performed on day 50 after birth. Lead exposure resulted in the potentiation of the LA effects of 5 mg/kg apomorphine without altering the LA effects of 50 mg/kg piribedil in group 1. Lead exposure resulted in an attenuation of the LA effects of apomorphine and piribedil in group 2. Lead exposure did not alter the K/sub D/ and B/sub max/ values of (/sup 3/H)spiperone in membranes prepared from the rat striatum or nucleus accumbens.

  11. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

    Science.gov (United States)

    Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

    1986-01-01

    In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

  12. Biogenic amines in brain areas of rats and response to varying dose levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Abdelhamid, F.M.; Elmossalamy, N.; Othman, S.A.; Roushdy, H.M.; Abdelraheem, K.

    1994-01-01

    The levels of norepinephrine (NE), dopamine (DA), 5-hydroxy-tryptamine (5-HT) and 5-hydroxy-indole acetic acid (5-HIAA) were examined in the brain areas:cortex,: cerebellum, striatum and pons in rats exposed to whole body gamma-irradiation at the dose levels 6.5 and 10 Gy. The data obtained indicated that: 6.5 Gy induced in all brain areas, a slight increase in 5-HT concomitant with significant decrease in NE, DA levels, besides a significant increase in 5-HTAA in cerebellum and pons. After the dose 10 Gy the maximum excitation of 5-HT level was in striatum whereas declines in NE, DA were recorded in all brain areas. 5-HIAA displayed significant increase in cerebellum and pons and maximum decline in the cortex. 4 tab

  13. Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson's Disease Induced by Rotenone.

    Science.gov (United States)

    Khadrawy, Yasser A; Salem, Ahmed M; El-Shamy, Karima A; Ahmed, Emad K; Fadl, Nevein N; Hosny, Eman N

    2017-09-03

    The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase. Rotenone induced a decrease in acetylcholinesterase and Na + /K + -ATPase activities and an increase in tumor necrosis factor-α level in the midbrain and the striatum. Protection and treatment with caffeine ameliorated the oxidative stress and the changes in acetylcholinesterase and Na + /K + -ATPase activities induced by rotenone in the midbrain and the striatum. This was associated with improvement in the histopathological changes induced in the two areas of PD model. Caffeine protection and treatment restored the depletion of midbrain and striatal dopamine induced by rotenone and prevented decline in motor activities (assessed by open field test) and muscular strength (assessed by traction and hanging tests) and improved norepinephrine level in the two areas. The present study showed that caffeine offered a significant neuroprotection and treatment against neurochemical, histopathological, and behavioral changes in a rotenone-induced rat model of PD.

  14. GSTpi expression in MPTP-induced dopaminergic neurodegeneration of C57BL/6 mouse midbrain and striatum.

    Science.gov (United States)

    Castro-Caldas, Margarida; Neves Carvalho, Andreia; Peixeiro, Isabel; Rodrigues, Elsa; Lechner, Maria Celeste; Gama, Maria João

    2009-06-01

    MPTP-induced dopaminergic neurotoxicity involves major biochemical processes such as oxidative stress and impaired energy metabolism, leading to a significant reduction in the number of nigrostriatal dopaminergic neurons. Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that provides protection of cells from injury by toxic chemicals and products of oxidative stress. In humans, polymorphisms of GSTP1 affect substrate selectivity and stability increasing the susceptibility to parkinsonism-inducing effects of environmental toxins. Given the ability of MPTP to increase the levels of reactive oxygen species and the link between altered redox potential and the expression and activity of GSTpi, we investigated the effect of MPTP on GSTpi cellular concentration in an in vivo model of Parkinson's disease. The present study demonstrates that GSTpi is actively expressed in both substantia nigra pars compacta and striatum of C57BL/6 mice brain, mostly in oligodendrocytes and astrocytes. After systemic administration of MPTP, GSTpi expression is significantly increased in glial cells in the vicinity of dopaminergic neurons cell bodies and fibers. The results suggest that GSTpi expression may be part of the mechanism underlying the ability of glial cells to elicit protection against the mechanisms involved in MPTP-induced neuronal death.

  15. Investigating the dynamics of the brain response to music: A central role of the ventral striatum/nucleus accumbens.

    Science.gov (United States)

    Mueller, Karsten; Fritz, Thomas; Mildner, Toralf; Richter, Maxi; Schulze, Katrin; Lepsien, Jöran; Schroeter, Matthias L; Möller, Harald E

    2015-08-01

    Ventral striatal activity has been previously shown to correspond well to reward value mediated by music. Here, we investigate the dynamic brain response to music and manipulated counterparts using functional magnetic resonance imaging (fMRI). Counterparts of musical excerpts were produced by either manipulating the consonance/dissonance of the musical fragments or playing them backwards (or both). Results show a greater involvement of the ventral striatum/nucleus accumbens both when contrasting listening to music that is perceived as pleasant and listening to a manipulated version perceived as unpleasant (backward dissonant), as well as in a parametric analysis for increasing pleasantness. Notably, both analyses yielded a ventral striatal response that was strongest during an early phase of stimulus presentation. A hippocampal response to the musical stimuli was also observed, and was largely mediated by processing differences between listening to forward and backward music. This hippocampal involvement was again strongest during the early response to the music. Auditory cortex activity was more strongly evoked by the original (pleasant) music compared to its manipulated counterparts, but did not display a similar decline of activation over time as subcortical activity. These findings rather suggest that the ventral striatal/nucleus accumbens response during music listening is strongest in the first seconds and then declines. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

    Science.gov (United States)

    Wittmann, Marc; Leland, David S; Paulus, Martin P

    2007-06-01

    Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter ( or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

  17. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance.

    Science.gov (United States)

    Innocenti, Giorgio M; Dyrby, Tim B; Andersen, Kasper Winther; Rouiller, Eric M; Caminiti, Roberto

    2017-06-01

    The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Differential Patterns of Amygdala and Ventral Striatum Activation Predict Gender-Specific Changes in Sexual Risk Behavior

    Science.gov (United States)

    Sansosti, Alexandra A.; Bowman, Hilary C.; Hariri, Ahmad R.

    2015-01-01

    Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior. PMID:26063921

  19. Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

    1986-06-01

    The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

  20. Proteomic Analysis of the Effect of Korean Red Ginseng in the Striatum of a Parkinson's Disease Mouse Model.

    Science.gov (United States)

    Kim, Dongsoo; Jeon, Hyongjun; Ryu, Sun; Koo, Sungtae; Ha, Ki-Tae; Kim, Seungtae

    2016-01-01

    Recent studies have shown that Korean Red Ginseng (KRG) suppresses dopaminergic neuronal death in the brain of a Parkinson's disease (PD) mouse model, but the mechanism is still elusive. Using a 2-dimensional electrophoresis technique, we investigated whether KRG can restore the changes in protein expressions in the striatum (ST) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Male C57BL/6 mice (9 weeks old) were injected with 20 mg/kg MPTP intraperitoneally four times at 2-h intervals. KRG (100 mg/kg) was orally administered once a day for 3 days from one hour after the first MPTP injection. Two hours after the third KRG administration a pole test was performed to evaluate motor function, after which the brains were immediately harvested. Survival of dopaminergic neurons in the nigrostriatal pathway and protein expression in the ST were measured by immunohistochemistry and 2-dimensional electrophoresis. KRG suppressed MPTP-induced behavioral dysfunction and neuronal death in the nigrostriatal pathway. Moreover, 30 proteins changed by MPTP and KRG in the ST were identified and shown to be related to glycolysis/gluconeogenesis and neurodegenerative diseases including Alzheimer's disease and PD. KRG has neuroprotective effects against MPTP toxicity and alleviates protein expression profiles related to enhancing energy metabolism in the ST of MPTP-treated mice.

  1. Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart

    International Nuclear Information System (INIS)

    Ross, S.B.; Renyi, A.L.

    1978-01-01

    The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3 H-dopamine (DA) in striatal slices and 3 H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of the 3 H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 times more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3 H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms. (author)

  2. Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

    Directory of Open Access Journals (Sweden)

    Svitlana Garbuzova-Davis

    Full Text Available Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas.In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO, significant BBB alterations characterized by large Evans Blue (EB parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices.These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.

  3. The effect of crack cocaine addiction on the microstructure and morphology of the human striatum and thalamus using novel shape analysis and fast diffusion kurtosis imaging

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A.; Mallar, Chakravarty; Hansen, Brian

    2016-01-01

    The striatum and thalamus are subcortical structures intimately involved in addiction, and the morphology and microstructure of these has been studied in murine models of cocaine addiction. However, human studies using non-invasive MRI has shown inconsistencies in morphology using volumetric...... analysis. In our study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC). We did not find....... Our findings suggest that the use of finer methods and sequences is needed to characterize morphological and microstructural changes in cocaine addiction, and that brain changes in cocaine addiction are related to age....

  4. Regional GABA concentration and [3H]-diazepam binding in rat brain following repeated electroconvulsive shock

    International Nuclear Information System (INIS)

    Bowdler, J.M.; Green, A.R.; Minchin, M.C.W.; Nutt, D.J.

    1983-01-01

    It has been confirmed that 24 hours following a series of electroconvulsive shocks (ECS) given once daily for 10 days (ECS x 10) to rats there is an increase in GABA concentration in the corpus striatum. A similar change was seen after the ECS had been given to rats anaesthetised with halothane, or when 5 ECS were given spread out over 10 days, the rats being anaesthetised during the ECS. A daily convulsion for 10 days elicited by flurothyl exposure resulted in an increased striatal GABA concentration, but also increased the GABA concentration in the hypothalamus, hippocampus and cortex. The increase in striatal GABA concentration was present 24 hours after ECS daily for 5 days or 3 days after ECS daily for 10 days. No change in [ 3 H]-diazepam binding was seen in hippocampus, cortex or corpus striatum 24 hours after the last of 10 once daily ECS. The increase in striatal GABA concentration was therefore seen at all times when enhanced monoaminemediated behaviours have been demonstrated following seizures. (Author)

  5. Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

    International Nuclear Information System (INIS)

    Inaji, Motoki; Okauchi, Takashi; Nagai, Yuji; Nojima, Kumie

    2003-01-01

    The present study was designed to make better Parkinson model animal and evaluate the transplantation treatment with ES cell. In the first year, we irradiated left striatum of adult rats with charged carbon particles (290 MeV/nucleon, 5 mm spread-out Bragg peak, 100 Gy) for purpose of making Parkinson model rats. At 4, 8, 12 weeks after the irradiation, we performed the rotation test to methamphetamine and the autoradiography on dopamine D2 receptor and transporter using 11 C-raclopride and 11 C-PE2I to measure the effects of the irradiation. As a result, the number of rotation increased and the distributions of dopamine D2 receptor and transporter in the striatum decreased during the time after the irradiation. These results suggested that the secondary neural damage due to the vascular degeneration caused the progressive destruction of dopamine system. To make more stable Parkinson model rats, we need to use smaller collimator and develop the accurate stereotactic irradiation system in the further research. (author)

  6. Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus.

    Science.gov (United States)

    Panaccione, Isabella; Iacovelli, Luisa; di Nuzzo, Luigi; Nardecchia, Francesca; Mauro, Gianluca; Janiri, Delfina; De Blasi, Antonio; Sani, Gabriele; Nicoletti, Ferdinando; Orlando, Rosamaria

    2017-03-01

    Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the prefrontal cortex or corpus striatum, as compared to both groups of control rats. No changes in the expression of mGlu3 receptor mRNA levels or mGlu1α and mGlu5 receptor protein levels were found with exception of an increase in mGlu1α receptor levels in the striatum of SD rats. Moving from these findings we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA (30mg/kg, i.p.). SD rats were also treated with sodium valproate (300mg/kg, i.p.) as an active comparator. Both BINA and sodium valproate were effective in reversing the manic-like phenotype evaluated in an open field arena in SD rats. BINA treatment had no effect on motor activity in control rats, suggesting that our findings were not biased by a non-specific motor-lowering activity of BINA. These findings suggest that changes in the expression of mGlu2 receptors may be associated with the enhanced motor activity observed with mania. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum.

    Science.gov (United States)

    Allen, Jeremy P; Hathway, Gareth J; Clarke, Neil J; Jowett, Mike I; Topps, Stephanie; Kendrick, Keith M; Humphrey, Patrick P A; Wilkinson, Lawrence S; Emson, Piers C

    2003-05-01

    The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.

  8. Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

    Science.gov (United States)

    Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

    2016-08-01

    Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. In vitro release of cholecystokinin octapeptide-like immunoreactivity from rat brain synaptosomes

    International Nuclear Information System (INIS)

    Klaff, L.J.; Hudson, A.; Sheppard, M.; Tyler, M.

    1981-01-01

    Enriched synaptosome fractions prepared by differential centrifugation and ultracentrifugation of homogenates of rat cortex, striatum, thalamus and hypothalamus contained over 65% of the total immunoreactive cholecystokinin octapeptide (CCK-8) in each area. A calcium dependent release of immunoreactive CCK-8 from these fractions in vitro in response to 2 depolarizing stimuli (60 mM KCl and 75 μM veratrine) has been demonstrated. Released CCK-8 immunoreactivity showed parallelism when serial dilutions were compared with the CCK-8 dose-response curve and eluted similarly to synthetic CCK-8 on Sephadex G-50 superfine chromatography. These results provide further evidence for a neurotransmitter or neuromodulator role for CCK-8 in brain

  10. Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age

    Directory of Open Access Journals (Sweden)

    James N. Porter

    2015-02-01

    Full Text Available The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns and dorsal anterior cingulate cortex (dACC that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

  11. Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

    Science.gov (United States)

    Sumiya, Motofumi; Koike, Takahiko; Okazaki, Shuntaro; Kitada, Ryo; Sadato, Norihiro

    2017-10-01

    Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Reward Anticipation in Ventral Striatum and Individual Sensitivity to Reward: A Pilot Study of a Child-Friendly fMRI Task.

    Science.gov (United States)

    van Hulst, Branko M; de Zeeuw, Patrick; Lupas, Kellina; Bos, Dienke J; Neggers, Sebastiaan F W; Durston, Sarah

    2015-01-01

    Reward processing has been implicated in developmental disorders. However, the classic task to probe reward anticipation, the monetary incentive delay task, has an abstract coding of reward and no storyline and may therefore be less appropriate for use with developmental populations. We modified the task to create a version appropriate for use with children. We investigated whether this child-friendly version could elicit ventral striatal activation during reward anticipation in typically developing children and young adolescents (aged 9.5-14.5). In addition, we tested whether our performance-based measure of reward sensitivity was associated with anticipatory activity in ventral striatum. Reward anticipation was related to activity in bilateral ventral striatum. Moreover, we found an association between individual reward sensitivity and activity in ventral striatum. We conclude that this task assesses ventral striatal activity in a child-friendly paradigm. The combination with a performance-based measure of reward sensitivity potentially makes the task a powerful tool for developmental imaging studies of reward processing.

  13. Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice

    Directory of Open Access Journals (Sweden)

    Muriel Laurent

    2017-12-01

    Full Text Available The striatum is a key brain structure involved in the processing of cognitive flexibility, which results from the balance between the flexibility demanded for novel learning of motor actions and the inflexibility required to preserve previously learned actions. In particular, the dorsolateral portion of the striatum (DLS is engaged in the learning of action sequence. This process is temporally driven by fine adjustments in the function of the two main neuronal populations of the striatum, known as the direct pathway medium spiny neurons (dMSNs and indirect pathway medium spiny neurons (iMSNs. Here, using optogenetics, behavioral, and electrophysiological tools, we addressed the relative role of both neuronal populations in the acquisition of a reversal dual action sequence in the DLS. While the channelrhodopsin-induced activation of dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the sequence, the specific activation of the dMSNs of the DLS facilitated the acquisition of a reversal dual action sequence; the activation of iMSNs induced a significant deficit in the acquisition of the same task. Taken together our results indicate an antagonistic relationship between dMSNs and iMSNs on the acquisition of a reversal dual action sequence.

  14. Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2018-01-01

    Full Text Available Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1, the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.

  15. Tracking of Neural Stem Cells in Rats with Intracerebral Hemorrhage by the Use of 3T MRI

    International Nuclear Information System (INIS)

    Chang, Nam Kyu; Jeong, Yong Yeon; Park, Jong Seong

    2008-01-01

    To access the feasibility of clinically available 3T MRI to detect the migration of labeled neural stem cells (NSCs) in intracerebral hemorrhage (ICH) in a rat model. The ethics committee of our institution approved this study. ICH was induced by the injection of collagenase type IV into the right striatum of ten Sprague-Dawley rats. Human NSCs conjugated with Feridex (superparamagnetic iron oxide: SPIO) were transplanted into the left striatum one week after ICH induction. MRI was performed on a 3T scanner during the first, second, third, fourth, and sixth weeks post-transplantation. MRI was obtained using coronal T2- and T2 * -weighted sequences. Two rats were sacrificed every week after in vivo MRI in order to analyze the histological findings. ICH in the right striatum was detected by MRI one and two weeks after transplantation without migration of the NSCs. There was no migration of the NSCs as seen on the histological findings one week after transplantation. The histological findings two weeks after transplantation showed a small number of NSCs along the corpus callosum. On MRI three weeks after transplantation, there was a hypointense line along the corpus callosum and decreased signal intensity in the right periventricular region. Histological findings three weeks after transplantation confirmed the presence of the hypointense line representing SPIO-labeled NSCs. MRI four and six weeks after transplantation showed a hypointense spot in the right periventricular region. The histological findings four and six weeks after transplantation showed the presence of prominent NSCs in the right periventricular region. 3T MRI can detect the migration of NSCs in rats with ICH along the corpus callosum. Therefore, 3T MRI could be feasible for detecting the migration of NSCs in the clinical setting of stem cell therapy

  16. Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat

    International Nuclear Information System (INIS)

    Reith, J.; Dyve, S.; Kuwabara, H.; Guttman, M.; Diksic, M.; Gjedde, A.

    1990-01-01

    In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. Donor rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into recipient rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum

  17. A response strategy predicts acquisition of schedule-induced polydipsia in rats.

    Science.gov (United States)

    Gregory, James Gardner; Hawken, Emily R; Banasikowski, Tomek J; Dumont, Eric C; Beninger, Richard J

    2015-08-03

    Schedule-induced polydipsia (SIP) is excessive, non-regulatory drinking. We aimed to identify phenotypic learning traits representative of neural circuitry that underlies SIP and hypothesized that rats that are response-learners will be more susceptible in developing compulsive water drinking. Using the Y-maze, the rats were characterized as either place- or response-learners. They were exposed to the SIP protocol for a period of 21days. Subsequent histological staining for FosB/ΔFosB examined neuronal activation associated with SIP in several brain regions. The rats with a preference for a response-learning strategy were more likely to develop SIP than the rats using a place-learning strategy. Furthermore amphetamine sensitization, observed to increase SIP, also shifted learning strategy to a response-learning strategy. No differences were observed in FosB/ΔFosB expression between SIP and non-SIP rats in the dorsolateral striatum (DLS) and CA1 region of the hippocampus. However, SIP rats had greater FosB/ΔFosB expression in prefrontal cortex regions. The rats that develop SIP have a preference for response-learning strategies and increased neuronal activation in frontal cortical regions associated with habit formation and compulsion. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Protective Effects of Ferulic Acid against Chronic Cerebral Hypoperfusion-Induced Swallowing Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Takashi Asano

    2017-03-01

    Full Text Available Ferulic acid (FA, a phenolic phytochemical, has been reported to exert antioxidative and neuroprotective effects. In this study, we investigated the protective effects of FA against the dysfunction of the swallowing reflex induced by ligation of bilateral common carotid arteries (2VO in rats. In 2VO rats, topical administration of water or citric acid to the pharyngolaryngeal region evoked a diminished number of swallowing events with prolonged latency compared to sham-operated control rats. 2VO rats had an increased level of superoxide anion radical, and decreased dopamine and tyrosine hydroxylase enzyme levels in the striatum, suggesting that 2VO augmented cerebral oxidative stress and impaired the striatal dopaminergic system. Furthermore, substance P (SP expression in the laryngopharyngeal mucosa, which is believed to be positively regulated by dopaminergic signaling in the basal ganglia, was decreased in 2VO rats. Oral treatment with FA (30 mg/kg for 3 weeks (from one week before 2VO to two weeks after improved the swallowing reflex and maintained levels of striatal dopamine and laryngopharyngeal SP expression in 2VO rats. These results suggest that FA maintains the swallowing reflex by protecting the dopamine-SP system against ischemia-induced oxidative damage in 2VO rats.

  19. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    Full Text Available Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase, breakdown (catechol-O-methyl transferase; monoamine oxygenase, transport [vesicular monoamine transporter (VMAT, dopamine transporter (DAT] and receptors (DRD1-D5] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen

  20. Effects of motion correction for dynamic [{sup 11}C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Choe, Yearn Seong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kang, Eun Joo [Kangwon University, Chunchon (Korea, Republic of)

    2005-10-15

    Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion

  1. Effects of motion correction for dynamic [11C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun; Choe, Yearn Seong; Kang, Eun Joo

    2005-01-01

    Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction

  2. Acetaminophen and aspirin inhibit superoxide anion generation and lipid peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats.

    Science.gov (United States)

    Maharaj, D S; Saravanan, K S; Maharaj, H; Mohanakumar, K P; Daya, S

    2004-04-01

    We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs inhibited cyanide-induced superoxide anion generation, as well as lipid peroxidation in rat brain homogenates, the combination of the agents resulting in a potentiation of this effect. Acetaminophen or aspirin when administered alone or in combination, did not alter dopamine (DA) levels in the forebrain or in the striatum. Intranigral infusion of MPP+ in rats caused severe depletion of striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic post-treatment of acetaminophen afforded partial protection, whereas similar treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA depletion. While these findings suggest usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.

  3. Treadmill Exercise Improves Motor Dysfunction and Hyperactivity of the Corticostriatal Glutamatergic Pathway in Rats with 6-OHDA-Induced Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2017-01-01

    Full Text Available Hyperactivity in the corticostriatal glutamatergic pathway (CGP induces basal ganglia dysfunction, contributing to parkinsonian syndrome (PS. Physical exercise can improve PS. However, the effect of exercise on the CGP, and whether this pathway is involved in the improvement of PS, remains unclear. Parkinson’s disease (PD was induced in rats by 6-hydroxydopamine injection into the right medial forebrain bundle. Motor function was assessed using the cylinder test. Striatal neuron (SN spontaneous and evoked firing activity was recorded, and the expression levels of Cav1.3 and CaMKII in the striatum were measured after 4 weeks of treadmill exercise. The motor function in PD rats was improved by treadmill exercise. SN showed significantly enhanced excitability, and treadmill exercise reduced SN excitability in PD rats. In addition, firing activity was evoked in SNs by stimulation of the primary motor cortex, and SNs exhibited significantly decreased stimulus threshold, increased firing rates, and reduced latency. The expression of Cav1.3 and p-CaMKII (Thr286 in the striatum were enhanced in PD rats. However, these