Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

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Kuswati

2015-04-01

Full Text Available Background Stress is one of the factors that cause apoptosis in neuronal cells. Centella asiatica has a neuroprotective effect that can inhibit apoptosis. This study aimed to examine the effect of Centella asiatica ethanol extract on B-cell lymphoma 2 (Bcl-2 protein expression in the prefrontal cortex of rats. Methods An experimental study was conducted on 34 brain tissue samples from male Sprague Dawley rats exposed to chronic restraint stress for 21 days. The samples were taken from following groups: non-stress group K, negative control group P1 (stress + arabic gum powder, P2 (stress + C.asiatica at 150 mg/kgBW, P3 (stress + C.asiatica at 300 mg/kg BW, P4 (stress + C.asiatica at 600 mg/kg body weight and positive control group P5 (stress + fluoxetine at 10 mg/kgBW. The samples were made into sections that were stained immunohistochemically using Bcl-2 antibody to determine the percentage of cells expressing Bcl-2. Data were analyzed using one way ANOVA test followed by a post - hoc test. Results There were significant differences in mean Bcl-2 expression between the groups receiving Centella asiatica compared with the non-stress group and stress-only group (negative control group (p<0.05. The results were comparable to those of the fluoxetine treatment group. Conclusion The Centella asiatica ethanol extract was able to increase Bcl-2 expression in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress. This study suggests that Centella asiatica may be useful in the treatment of cerebral stress.

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

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Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

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Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

2014-01-01

The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

Slower gait, slower information processing and smaller prefrontal area in older adults.

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Rosano, C.; Studenski, S.A.; Aizenstein, H.J.; Boudreau, R.M.; Longstreth Jr, W.T.; Newman, A.B.

2012-01-01

BACKGROUND: Slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and

Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

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Dela Peña, Ike; Dela Peña, Irene Joy; de la Peña, June Bryan; Kim, Hee Jin; Shin, Chan Young; Han, Doug Hyun; Kim, Bung-Nyun; Ryu, Jong Hoon; Cheong, Jae Hoon

2017-09-01

Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function

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Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; De Boer, Sietse F.; Koolhaas, Jaap M.; Meerlo, Peter

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly

PI[subscript 3]-Kinase Cascade Has a Differential Role in Acquisition and Extinction of Conditioned Fear Memory in Juvenile and Adult Rats

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Slouzkey, Ilana; Maroun, Mouna

2016-01-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (P[subscript 3]K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear…

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Yi-Yun Liu

Full Text Available Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT, open field test (OFT, elevated plus maze (EPM and forced swim test (FST were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex are necessary for odor span in rats

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Don A Davies

2013-12-01

Full Text Available Working memory is a type of short-term memory involved in the maintenance and manipulation of information essential for complex cognition. While memory span capacity has been extensively studied in humans as a measure of working memory, it has received considerably less attention in rodents. Our aim was to examine the role of the NMDA and AMPA glutamate receptors in odor span capacity using systemic injections or infusions of receptor antagonists into the medial prefrontal cortex. Long Evans rats were trained on a well-characterized odor span task. Initially, rats were trained to dig for a food reward in sand followed by training on a non-match to sample discrimination using sand scented with household spices. The rats were then required to perform a serial delayed non-match to sample procedure which was their odor span. Systemic injection of the broad spectrum NMDA receptor antagonist CPP (10 mg/kg or the GluN2B-selective antagonist Ro25-6981 (10 mg/kg but not 6 mg/kg significantly reduced odor span capacity. Infusions of the GluN2B- selective antagonist Ro25-6981 (2.5 µg/hemisphere into medial prefrontal cortex reduced span capacity, an effect that was nearly significant (p = 0.069. Infusions of the AMPA receptor antagonist CNQX (1.25 µg/hemisphere into medial prefrontal cortex reduced span capacity and latency for the rats to make a choice in the task. These results demonstrate span capacity in rats depends on ionotropic glutamate receptor activation in the medial prefrontal cortex. Further understanding of the circuitry underlying span capacity may aid in the novel therapeutic drug development for persons with working memory impairments as a result of disorders such as schizophrenia and Alzheimer’s disease.

Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

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Roelf J. Cruz-Rizzolo

2017-12-01

Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

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Maurício dos Santos Pereira

Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

Adolescent Social Stress Produces an Enduring Activation of the Rat Locus Coeruleus and Alters its Coherence with the Prefrontal Cortex

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Zitnik, Gerard A; Curtis, Andrè L; Wood, Susan K; Arner, Jay; Valentino, Rita J

2016-01-01

Early life stress is associated with the development of psychiatric disorders. Because the locus coeruleus-norepinephrine (LC-NE) system is a major stress-response system that is implicated in psychopathology, developmental differences in the response of this system to stress may contribute to increased vulnerability. Here LC single unit and network activity were compared between adult and adolescent rats during resident-intruder stress. In some rats, LC and medial prefrontal cortex (mPFC) coherence was quantified. The initial stress tonically activated LC neurons and induced theta oscillations, while simultaneously decreasing LC auditory-evoked responses in both age groups. Stress increased LC-mPFC coherence within the theta range. With repeated exposures, adolescent LC neuronal and network activity remained elevated even in the absence of the stressor and were unresponsive to stressor presentation. In contrast, LC neurons of adult rats exposed to repeated social stress were relatively inhibited in the absence of the stressor and mounted robust responses upon stressor presentation. LC sensory-evoked responses were selectively blunted in adolescent rats exposed to repeated social stress. Finally, repeated stress decreased LC-mPFC coherence in the high frequency range (beta and gamma) while maintaining strong coherence in the theta range, selectively in adolescents. Together, these results suggest that adaptive mechanisms that promote stress recovery and maintain basal activity of the brain norepinephrine system in the absence of stress are not fully developed or are vulnerable stress-induced impairments in adolescence. The resulting sustained activation of the LC-NE system after repeated social stress may adversely impact cognition and future social behavior of adolescents. PMID:26361057

Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

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Thomas F Giustino

Full Text Available The medial prefrontal cortex (mPFC plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL and infralimbic (IL subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition. This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both

Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

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Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

2017-06-15

TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

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Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

2015-08-20

Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

Institute of Scientific and Technical Information of China (English)

Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi

2013-01-01

Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9％ NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

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Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

2014-01-01

Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults

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Ayaka Ishii-Takahashi

2014-01-01

Full Text Available The differential diagnosis of autism spectrum disorders (ASDs and attention deficit hyperactivity disorder (ADHD based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.

Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

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Yamada, Makiko; Kawahara, Yukie; Kaneko, Fumi; Kishikawa, Yuki; Sotogaku, Naoki; Poppinga, Wilfred J.; Folgering, Joost H. A.; Dremencov, Eliyahu; Kawahara, Hiroshi; Nishi, Akinori

Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC

Impact of Environmental Enrichment on Perineuronal Nets in the Prefrontal Cortex following Early and Late Abstinence from Sucrose Self-Administration in Rats.

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Megan Slaker

Full Text Available Perineuronal nets (PNNs are aggregates of extracellular matrix that form structures surrounding a subset of GABAergic interneurons. The staining intensity of PNNs appears to be related to plasticity. Environmental enrichment (EE influences plasticity during adulthood: EE decreases the rewarding effects of drugs of abuse and diminishes both drug- and sucrose-seeking behavior. We determined the impact of EE on PNN intensity in the medial prefrontal cortex (mPFC in rats trained to self-administer sucrose. We examined the number and intensity of PNNs within the prelimbic (PL, infralimbic (IL, and orbitofrontal (OF regions of the mPFC of adult Long-Evans rats that were trained for sucrose self-administration followed by acute or chronic EE during abstinence and a cue-induced reinstatement test. Rats exposed to EE prior to a cue-induced reinstatement of sucrose seeking had an increase in PNN staining compared with rats in standard housing. Conversely, naïve rats given 1 day of EE had a decrease in PNN intensity in the PL, no change in the IL, and an increase in the OF. Our findings demonstrate that EE increases PNN intensity in the mPFC after sucrose training, suggesting that training enhances the ability of EE to increase PNN intensity. We further demonstrate an interaction between time of abstinence, duration of EE exposure, and cue-induced reinstatement. Our results suggest that increased PNN intensity after EE may alter the excitatory/inhibitory balance of mPFC neurons such that rats are less responsive to a sucrose cue.

Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

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Laura Musazzi

2010-01-01

Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats

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Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole

2017-01-01

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of...... in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease.......Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim...... that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia.NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead...

[The administration of interleukin-1beta during early postnatal develop ment impairs FGF2, but not TIMP1, mRNA expression in brain structures of adult rats].

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Trofimov, A N; Zubareva, O E; Shvarts, A P; Ishchenko, A M; Klimenko, V M

2014-09-01

According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.

Projection from the prefrontal cortex to histaminergic cell groups in the posterior hypothalamic region of the rat. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunocytochemistry of histidine decarboxylase

NARCIS (Netherlands)

Wouterlood, F.G.; Steinbusch, H.W.M.; Luiten, P.G.M.; Bol, J.G.J.M.

1987-01-01

We investigated the projection from the infralimbic division of the prefrontal cortex (area 25) to histaminergic neurons in the posterior hypothalamic area. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in the prefrontal cortex of rats. Frozen brain sections were subjected to combined

Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

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Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

2017-05-23

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

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Chunmei Guo

2010-01-01

Full Text Available Neonatal blockade of N-methyl-D-aspartic acid (NMDA receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.

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Zhou, Xinyu; Liu, Lanxiang; Zhang, Yuqing; Pu, Juncai; Yang, Lining; Zhou, Chanjuan; Yuan, Shuai; Zhang, Hanping; Xie, Peng

2017-02-20

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

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Maren Strenziok

Full Text Available Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

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Strenziok, Maren; Greenwood, Pamela M; Santa Cruz, Sophia A; Thompson, James C; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to

Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex.

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Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Jastrzębska, Joanna; Wydra, Karolina; Miszkiel, Joanna; Sanak, Marek; Filip, Małgorzata

2017-07-01

Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required.

Back to front: cerebellar connections and interactions with the prefrontal cortex

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Thomas C Watson

2014-02-01

Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

The medial prefrontal cortex and memory of cue location in the rat.

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Rawson, Tim; O'Kane, Michael; Talk, Andrew

2010-01-01

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory. Copyright 2009 Elsevier Inc. All rights reserved.

Uptake of trace elements in adult and suckling rat lenses

International Nuclear Information System (INIS)

Nabekura, Tomohiro; Ito, Yoshimasa; Minami, Takeshi; Hirunuma, Rieko; Enomoto, Shuichi

2001-01-01

The uptake of trace elements in the lens was compared in adult and suckling rat lenses. Multitracers, including 15 trace elements, As, Be, Co, Fe, Mn, Rb, Rh, Ru, Sc, Se, Sr, Y, V, Zn, and Zr, were incubated with the lenses for 4 hr and their concentrations in the lens were measured. A high uptake rate of Zn was observed in the lenses of both adult and suckling rats in comparison with those of the other elements, and the Zn concentration in the lens of suckling rats was higher than that of adult rats. The uptake rate of Sr was higher in adult rats than in suckling rats. On the other contrary, Rb and Se concentrations in the lens were higher in suckling rats than in adult rats. The present study suggests that the different mechanisms depending on development serve to transport trace elements into the lens. (author)

Impaired prefrontal hemodynamic maturation in autism and unaffected siblings.

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Yuki Kawakubo

Full Text Available BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD. Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb] in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena.

The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

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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.

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

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Sullivan, R M

2004-06-01

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Radiation nephropathy in young and adult rats

International Nuclear Information System (INIS)

Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

1987-01-01

The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

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Nair, Sunila G; Gudelsky, Gary A

2004-09-15

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults.

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Koestner, Bryan P; Hedgcock, William; Halfmann, Kameko; Denburg, Natalie L

2016-01-01

Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment.

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Tomoda, Akemi; Suzuki, Hanako; Rabi, Keren; Sheu, Yi-Shin; Polcari, Ann; Teicher, Martin H

2009-08-01

Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). 1455 young adults (18-25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P=0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P=0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA24) (P<0.001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.

Effects of medial prefrontal cortex lesions in rats on the what-where-when memory of a fear conditioning event.

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Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min

2011-03-17

Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.

Khat distorts the prefrontal cortex histology and function of adult ...

African Journals Online (AJOL)

Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

Fluvoxamine maleate effects on dopamine signaling in the prefrontal cortex of stressed Parkinsonian rats: Implications for learning and memory.

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Dallé, Ernest; Daniels, Willie M U; Mabandla, Musa V

2017-06-01

Parkinson's disease (PD) is also associated with cognitive impairment and reduced extrinsic supply of dopamine (DA) to the prefrontal cortex (PFC). In the present study, we looked at whether exposure to early life stress reduces DA and serotonin (5-HT) concentration in the PFC thus leading to enhanced cognitive impairment in a Parkinsonian rat model. Maternal separation was the stressor used to develop an animal model for early life stress that has chronic effects on brain and behavior. Sprague-Dawley rats were treated with the antidepressant Fluvoxamine maleate (FM) prior to a unilateral 6-hydroxydopamine (6-OHDA) lesion to model motor deficits in rats. The Morris water maze (MWM) and the forelimb use asymmetry (cylinder) tests were used to assess learning and memory impairment and motor deficits respectively. Blood plasma was used to measure corticosterone concentration and prefrontal tissue was collected for lipid peroxidation, DA, and 5-HT analysis. Our results show that animals exposed to early life stress displayed learning and memory impairment as well as elevated basal plasma corticosterone concentration which were attenuated by treatment with FM. A 6-OHDA lesion effect was evidenced by impairment in the cylinder test as well as decreased DA and 5-HT concentration in the PFC. These effects were attenuated by FM treatment resulting in higher DA concentration in the PFC of treated animals than in non-treated animals. This study suggests that DA and 5-HT signaling in the PFC are responsive to FM and may reduce stress-induced cognitive impairment in PD. Copyright © 2017. Published by Elsevier Inc.

Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence

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Yu Zhang

2017-01-01

Full Text Available Using a valid chronic mild stress (CMS model of depression, we found that adolescent (postnatal days [PND] 28–41 CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB and brain-derived neurotrophic factor (BDNF in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression.

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

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Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

2017-01-01

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

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Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

2015-08-01

Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

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Zimbo Saroeni Raymond Maria Boudewijns

2013-06-01

Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Towards the therapeutics of cognitive impairment of schizophrenia

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Takashi eUehara

2014-09-01

Full Text Available Rationale Augmentation therapy with serotonin-1A (5-HT1A receptor partial agonists has been suggested to improve cognitive deficits in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production.Objectives and methods The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days of tandospirone (0.05 and 5 mg/kg on brain energy metabolism, as represented by extracellular lactate concentration (eLAC in the medial prefrontal cortex (mPFC of young adult rats..Results Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot shock stress (FS. Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment.Conclusions These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism based on brain energy metabolism by which 5-HT1A agonism improve cognitive impairment in schizophrenia and related disorders.

Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment.

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Peiqi Wang

Full Text Available Postoperative cognitive dysfunction (POCD is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1 activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1 were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and

Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment.

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Wang, Peiqi; Cao, Jiangbei; Liu, Na; Ma, Li; Zhou, Xueyue; Zhang, Hong; Wang, Yongan

2016-01-01

Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1) activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1) were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and prefrontal cortices of

Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

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Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

2010-01-01

Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

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Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P CSR rats (P CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices.

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Rebai, Redouane; Jasmin, Luc; Boudah, Abdennacer

2017-09-01

In the past few years possible mechanisms that link diabetes and depression have been found. One of these mechanisms is the increase in lipid peroxidation and decrease in antioxidant activity in the hippocampal and prefrontal cortices, which are brain areas involved in mood. The goal of the present study was to evaluate the effect of an antidepressant and of an antioxidant on behavior and oxidative activity in brains of diabetic rats. Rats rendered diabetic after a treatment with streptozotocin (STZ) (60mg/kg) were treated with fluoxetine (15mg/kg), melatonin (10mg/kg), or vehicle for 4 weeks. All animals were tested for signs of depression and anxiety using the elevated plus maze (EPM), open field test (OFT) and the forced swim test (FST). Four groups were compared: (1) normoglycemic, (2) hyperglycemic vehicle treated, and hyperglycemic (3) fluoxetine or (4) melatonin treated rats. On the last day of the study, blood samples were obtained to determine the levels of hemoglobin A1c (HbA1c). Also, brain samples were collected to measure the oxidative stress in the hippocampal and prefrontal cortices using the thiobarbituric acid reactive substances (TBARS) assay. The activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were also measured on the brain samples. The results show that both fluoxetine and melatonin decrease the signs of depression and anxiety in all tests. Concomitantly, the levels of HbA1c were reduced in drug treated rats, and to a greater degree in the fluoxetine group. In the cerebral cortex of diabetic rats, TBARS was increased, while the activity of CAT, GPx and GST were decreased. Fluoxetine and melatonin treatments decreased TBARS in both cortices. In the prefrontal cortex, fluoxetine and melatonin restored the activity of CAT, while only melatonin improved the activity of GPx and GST. In the hippocampus, the activity of GPx alone was restored by melatonin, while fluoxetine had no

Directional hippocampal-prefrontal interactions during working memory.

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Liu, Tiaotiao; Bai, Wenwen; Xia, Mi; Tian, Xin

2018-02-15

Working memory refers to a system that is essential for performing complex cognitive tasks such as reasoning, comprehension and learning. Evidence shows that hippocampus (HPC) and prefrontal cortex (PFC) play important roles in working memory. The HPC-PFC interaction via theta-band oscillatory synchronization is critical for successful execution of working memory. However, whether one brain region is leading or lagging relative to another is still unclear. Therefore, in the present study, we simultaneously recorded local field potentials (LFPs) from rat ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) and while the rats performed a Y-maze working memory task. We then applied instantaneous amplitudes cross-correlation method to calculate the time lag between PFC and vHPC to explore the functional dynamics of the HPC-PFC interaction. Our results showed a strong lead from vHPC to mPFC preceded an animal's correct choice during the working memory task. These findings suggest the vHPC-leading interaction contributes to the successful execution of working memory. Copyright © 2017. Published by Elsevier B.V.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

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Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Sex differences in social interaction behaviors in rats are mediated by extracellular signal-regulated kinase 2 expression in the medial prefrontal cortex

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Carrier, Nicole; Kabbaj, Mohamed

2012-01-01

Considerable sex differences occur in the incidence and prevalence of anxiety disorders where women are more anxious than men, particularly in situations where social interaction is required. In preclinical studies, the social interaction test represents a valid animal model to study sex differences in social anxiety. Indeed, female rats engage less in conspecific interactions than their male counterparts, which are behaviors indicative of higher social anxiety in female rats. In this work, we implicated extracellular signal regulated kinase 2 (ERK2) in the medial prefrontal cortex (mPFC) in mediating social interaction. Indeed, female rats’ had lower ERK2 expression compared to male rats, and overexpression of ERK2 in the mPFC increases their social interaction to the level seen in their male counterparts. These data indicate that the sexually dimorphic expression of ERK2 mediates social anxiety-like behaviors. PMID:22521590

The role of the medial prefrontal cortex in the play fighting of rats.

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Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

2009-12-01

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

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Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

2016-01-01

Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat.

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Basso, Julia C; Morrell, Joan I

2015-08-01

Voluntary wheel running in rats provides a preclinical model of exercise motivation in humans. We hypothesized that rats run because this activity has positive incentive salience in both the acquisition and habitual stages of wheel running and that gender differences might be present. Additionally, we sought to determine which forebrain regions are essential for the motivational processes underlying wheel running in rats. The motivation for voluntary wheel running in male and female Sprague-Dawley rats was investigated during the acquisition (Days 1-7) and habitual phases (after Day 21) of running using conditioned place preference (CPP) and the reinstatement (rebound) response after forced abstinence, respectively. Both genders displayed a strong CPP for the acquisition phase and a strong rebound response to wheel deprivation during the habitual phase, suggesting that both phases of wheel running are rewarding for both sexes. Female rats showed a 1.5 times greater rebound response than males to wheel deprivation in the habitual phase of running, while during the acquisition phase, no gender differences in CPP were found. We transiently inactivated the medial prefrontal cortex (mPFC) or the nucleus accumbens (NA), hypothesizing that because these regions are involved in the acquisition and reinstatement of self-administration of both natural and pharmacological stimuli, they might also serve a role in the motivation to wheel run. Inactivation of either structure decreased the rebound response in the habitual phase of running, demonstrating that these structures are involved in the motivation for this behavior. (c) 2015 APA, all rights reserved).

GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.

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Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken; Mena, Jesus D

2016-03-01

A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

Individual Differences in Reasoning and Visuospatial Attention are Associated with Prefrontal and Parietal White Matter Tracts in Healthy Older Adults

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Monge, Zachary A.; Greenwood, Pamela M.; Parasuraman, Raja; Strenziok, Maren

2016-01-01

Objective Although reasoning and attention are two cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. Method Sixty-one adults aged 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess Fractional Anisotropy (FA) – a measure of white matter integrity. A principle component analysis of the test scores yielded two components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. Results For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract, and bilateral parietal and temporal connections were found. Conclusions We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. PMID:26986750

From adolescent to elder rats: Motivation for palatable food and cannabinoids receptors.

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Amancio-Belmont, Octavio; Romano-López, Antonio; Ruiz-Contreras, Alejandra Evelin; Méndez-Díaz, Mónica; Prospéro-García, Oscar

2017-09-01

To analyze motivation, food self-administration and decision-making were evaluated in adolescent, adult, and aged rats. Subjects were trained to press a lever (fixed ratio, FR1 and FR5) in an operant chamber, to obtain chocolate flavor pellets. They assessed the progressive ratio (PR), extinction, and reinstatement of the behavior. To estimate decision-making for food, rats were trained in the conditioned place preference (CPP) paradigm: (a) associating one compartment with lab chow (LCh) one day and the other compartment with rice krisspies (RK), the next day. (b) Training similar to (a) but on the day RK was the reinforcer, it was delivered with a progressive delay. In addition, CB1 and CB2 receptor expression in the nucleus accumbens (NAcc) and prefrontal cortex (PFC) was estimated by means of Western blot. Adolescent rats consumed higher amounts of RK/body weight than adult and aged rats during FR1, FR5, and PR. Extinction was more prolonged for adolescent rats than for adult and aged rats. First CPP condition, all three groups of rats preferred the RK-associated compartment. Second CPP condition, adolescent rats developed equal preference to both compartments, while adult and aged rats preferred the RK-associated compartment. Rats per group ate a similar amount of either reinforcer. Adolescent rats exhibited low expression of CB1R in the NAcc and low expression of both CB1R and CB2R in the PFC compared with adult and aged rats. Adolescent rats display higher motivation for palatable food and an indiscriminate seeking behavior suggesting involvement of both homeostatic and hedonic systems in their decision-making processes. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 917-927, 2017. © 2016 Wiley Periodicals, Inc.

Prefrontal cortex activation during obstacle negotiation: What's the effect size and timing?

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Maidan, Inbal; Shustak, Shiran; Sharon, Topaz; Bernad-Elazari, Hagar; Geffen, Nimrod; Giladi, Nir; Hausdorff, Jeffrey M; Mirelman, Anat

2018-04-01

Obstacle negotiation is a daily activity that requires the integration of sensorimotor and cognitive information. Recent studies provide evidence for the important role of prefrontal cortex during obstacle negotiation. We aimed to explore the effects of obstacle height and available response time on prefrontal activation. Twenty healthy young adults (age: 30.1 ± 1.0 years; 50% women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 50 mm and 100 mm. Prefrontal activation was measured using a functional near-infrared spectroscopy system. Kinect cameras measured the obstacle negotiation strategy. Prefrontal activation was defined based on mean level of HbO 2 before, during and after obstacle negotiation and the HbO 2 slope from gait initiation and throughout the task. Changes between types of obstacles were assessed using linear-mix models and partial correlation analyses evaluated the relationship between prefrontal activation and the distance between the feet as the subjects traversed the obstacles. Different obstacle heights showed similar changes in prefrontal activation measures (p > 0.210). However, during unanticipated obstacles, the slope of the HbO 2 response was steeper (p = 0.048), as compared to anticipated obstacles. These changes in prefrontal activation during negotiation of unanticipated obstacles were correlated with greater distance of the leading foot after the obstacles (r = 0.831, p = 0.041). These findings are the first to show that the pattern of prefrontal activation depends on the nature of the obstacle. More specifically, during unanticipated obstacles the recruitment of the prefrontal cortex is faster and greater than during negotiating anticipated obstacles. These results provide evidence of the important role of the prefrontal cortex and the ability of healthy young adults to tailor the activation pattern to different types of obstacles. Copyright © 2018

Influence of iron on plutonium absorption by the adult and neonatal rat

International Nuclear Information System (INIS)

Sullivan, M.F.; Ruemmler, P.S.; Buschbom, R.L.

1986-01-01

To determine how iron affects plutonium absorption, adult rats were gavaged with 238 Pu nitrate (pH 2) after they had been fed an iron-deficient diet or treated with iron supplements. Neonatal rats born to dams on an iron-deficient diet were also gavaged with 238 Pu. An iron-deficient diet resulted in enhanced 238 Pu absorption both in the adults and in neonates born to iron-deficient dams. Ferric iron increased 238 Pu absorption 12-fold in adult rats; injected iron-dextran reduced that increase; gavaged ferrous iron reduced 238 Pu absorption to one-third of the control value. Rat neonates absorbed 30 to 40 times as much 238 Pu as adults; absorption was lowered in groups that received iron supplements: Iron-dextran caused a 50% reduction; ferric iron, 95%; and ferrous iron, greater than 95%. The results demonstrate an effect of the oxidation state of iron on plutonium absorption in adult rats different from that observed in suckling rats. The results suggest that the high rate of 238 Pu absorption by neonatal animals is due not only to the permeability of their intestines but also to their high demand for iron

Reduced expression of Nogo-A leads to motivational deficits in rats

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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.

Blockade of α2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment.

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Baskin, Britahny M; Nic Dhonnchadha, Bríd Á; Dwoskin, Linda P; Kantak, Kathleen M

2017-10-01

Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. Following treatment from postnatal days 28-55 with atomoxetine (0.3 mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3 mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10-56 μg/side) directly into prelimbic cortex. Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.

[Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

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Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

2017-12-01

Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

Prenatal alcohol exposure alters gene expression in the rat brain: Experimental design and bioinformatic analysis of microarray data

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Alexandre A. Lussier

2015-09-01

Full Text Available We previously identified gene expression changes in the prefrontal cortex and hippocampus of rats prenatally exposed to alcohol under both steady-state and challenge conditions (Lussier et al., 2015, Alcohol.: Clin. Exp. Res., 39, 251–261. In this study, adult female rats from three prenatal treatment groups (ad libitum-fed control, pair-fed, and ethanol-fed were injected with physiological saline solution or complete Freund׳s adjuvant (CFA to induce arthritis (adjuvant-induced arthritis, AA. The prefrontal cortex and hippocampus were collected 16 days (peak of arthritis or 39 days (during recovery following injection, and whole genome gene expression was assayed using Illumina׳s RatRef-12 expression microarray. Here, we provide additional metadata, detailed explanations of data pre-processing steps and quality control, as well as a basic framework for the bioinformatic analyses performed. The datasets from this study are publicly available on the GEO repository (accession number GSE63561.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

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Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

2016-09-01

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

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Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

2007-01-01

Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

Decline of prefrontal cortical-mediated executive functions but attenuated delay discounting in aged Fischer 344 × brown Norway hybrid rats.

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Hernandez, Caesar M; Vetere, Lauren M; Orsini, Caitlin A; McQuail, Joseph A; Maurer, Andrew P; Burke, Sara N; Setlow, Barry; Bizon, Jennifer L

2017-12-01

Despite the fact that prefrontal cortex (PFC) function declines with age, aged individuals generally show an enhanced ability to delay gratification, as evident by less discounting of delayed rewards in intertemporal choice tasks. The present study was designed to evaluate relationships between 2 aspects of PFC-dependent cognition (working memory and cognitive flexibility) and intertemporal choice in young (6 months) and aged (24 months) Fischer 344 × brown Norway F1 hybrid rats. Rats were also evaluated for motivation to earn rewards using a progressive ratio task. As previously reported, aged rats showed attenuated discounting of delayed rewards, impaired working memory, and impaired cognitive flexibility compared with young. Among aged rats, greater choice of delayed reward was associated with preserved working memory, impaired cognitive flexibility, and less motivation to work for food. These relationships suggest that age-related changes in PFC and incentive motivation contribute to variance in intertemporal choice within the aged population. Cognitive impairments mediated by PFC are unlikely, however, to fully account for the enhanced ability to delay gratification that accompanies aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

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Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

2015-12-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex

In vitro uptake of 75Se-selenite by lens of young and adult rats

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Sladkova, J.; Ostadalova, I.; Babicky, A.; Obenberger, J.

1988-01-01

The uptake was observed of 75 Se-selenite by the lens in Wistar strain rats in adult animals, in 17-day old rats kept with their mothers and in prematurely weaned rats. Also measured was the excretion of 75 Se by the lens of young and adult rats following incubation in the medium with radioselenium. The metabolites were analysed which were discharged by the lens containing 75 Se. In Brattleboro rats the uptake of 75 Se-selenite was also measured by the lens in young and adult rats. The uptake of 75 Se-selenite by the lens in young Wistar rats was found to be 1.6 times higher than by the lens of adult rats and the time course of the radioselenium uptake was slightly different. In the lens of prematurely weaned rats no significant difference was found in the uptake of radioselenium after 4 hours as compared with rats of the same age kept with their mothers. In homozygous Brattleboro rats, a higher uptake of 75 Se-selenite was found as compared with both young and adult heterozygous rats. The time course and the quantity of 75 Se efflux from the lens of young and adult Wistar rats differed significantly after 0.5 hour of pre-incubation. From metabolites containing 75 Se excreted by the lens following preincubation, glutathione selenotrisulfide and a not yet accurately determined fraction with a large share of radioactivity were isolated. The stated results provide yet more proof that selenium cataract is a manifestation of the ontogenic dependence of selenium metabolism in the lens and in the entire organism. (author). 4 tabs., 30 refs

Prefrontal and parietal correlates of cognitive control related to the adult outcome of attention-deficit/hyperactivity disorder diagnosed in childhood.

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Schulz, Kurt P; Li, Xiaobo; Clerkin, Suzanne M; Fan, Jin; Berwid, Olga G; Newcorn, Jeffrey H; Halperin, Jeffrey M

2017-05-01

The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

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Li, Y Q; Wong, C S

2000-09-01

This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

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Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

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Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Computational modelling and analysis of hippocampal-prefrontal information coding during a spatial decision-making task

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Thomas eJahans-Price

2014-03-01

Full Text Available We introduce a computational model describing rat behaviour and the interactions of neural populations processing spatial and mnemonic information during a maze-based, decision-making task. The model integrates sensory input and implements a working memory to inform decisions at a choice point, reproducing rat behavioural data and predicting the occurrence of turn- and memory-dependent activity in neuronal networks supporting task performance. We tested these model predictions using a new software toolbox (Maze Query Language, MQL to analyse activity of medial prefrontal cortical (mPFC and dorsal hippocampal (dCA1 neurons recorded from 6 adult rats during task performance. The firing rates of dCA1 neurons discriminated context (i.e. the direction of the previous turn, whilst a subset of mPFC neurons was selective for current turn direction or context, with some conjunctively encoding both. mPFC turn-selective neurons displayed a ramping of activity on approach to the decision turn and turn-selectivity in mPFC was significantly reduced during error trials. These analyses complement data from neurophysiological recordings in non-human primates indicating that firing rates of cortical neurons correlate with integration of sensory evidence used to inform decision-making.

Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

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Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

2015-01-01

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

Structural Variation within the Amygdala and Ventromedial Prefrontal Cortex Predict Memory for Impressions in Older Adults

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Brittany Shane Cassidy

2012-08-01

Full Text Available Research has shown that lesions to regions involved in social and emotional cognition disrupt socioemotional processing and memory. We investigated how structural variation of regions involved in socioemotional memory (ventromedial prefrontal cortex [vmPFC], amygdala, as opposed to a region implicated in explicit memory (hippocampus, affected memory for impressions in young and older adults. Anatomical MRI scans for fifteen young and fifteen older adults were obtained and reconstructed to gather information about cortical thickness and subcortical volume. Young adults had greater amygdala and hippocampus volumes than old, and thicker left vmPFC than old, although right vmPFC thickness did not differ across the age groups. Participants formed behavior-based impressions and responded to interpersonally meaningful, social but interpersonally irrelevant, or non-social prompts, and completed a memory test. Results showed that greater left amygdala volume predicted enhanced overall memory for impressions in older but not younger adults. Increased right vmPFC thickness in older, but not younger, adults correlated with enhanced memory for impressions formed in the interpersonally meaningful context. Hippocampal volume was not predictive of social memory in young or older adults. These findings demonstrate the importance of structural variation in regions linked to socioemotional processing in the retention of impressions with age, and suggest that the amygdala and vmPFC play an integral role when encoding and retrieving social information.

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

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Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine

Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

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Judith R Homberg

Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

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

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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.

Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

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Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

2016-02-01

Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety-like behaviors

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Letícia Scheidt

2015-09-01

Full Text Available Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36 were housed in groups of four until postnatal day (PND 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16, 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12, or water (n = 12 every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test and anxiety-like behaviors (elevated plus maze during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

International Nuclear Information System (INIS)

Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

2010-01-01

Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 μg/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 μg/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

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Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Kinetics of lead retention and distribution in suckling and adult rats

International Nuclear Information System (INIS)

Momcilovic, B.; Kostial, K.

1974-01-01

The kinetics of lead distribution was studied in suckling and adult rats 8 days after a single intraperitoneal injection of 203 Pb. Marked differences were observed in the kinetics of lead retention and distribution in suckling as compared to adult rats. The rate of 203 Pb disappearance was lower in the whole body, blood and kidneys, but higher in the liver, while the deposition processes predominated in the brain, femur and teeth of sucklings as compared to adult animals. (auth)

Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

Energy Technology Data Exchange (ETDEWEB)

Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

Hypertension after bilateral kidney irradiation in young and adult rats

International Nuclear Information System (INIS)

Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

1987-01-01

The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

Adjunctive Treatment with Asenapine Augments the Escitalopram-Induced Effects on Monoaminergic Outflow and Glutamatergic Neurotransmission in the Medial Prefrontal Cortex of the Rat

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Björkholm, Carl; Frånberg, Olivia; Malmerfelt, Anna; Marcus, Monica M.; Konradsson-Geuken, Åsa; Schilström, Björn; Jardemark, Kent

2015-01-01

Background: Substantial clinical data support the addition of low doses of atypical antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) to rapidly enhance the antidepressant effect in treatment-resistant depression. Preclinical studies suggest that this effect is at least partly explained by an increased catecholamine outflow in the medial prefrontal cortex (mPFC). Methods: In the present study we used in vivo microdialysis in freely moving rats and in vitro intracellular recordings of pyramidal cells of the rat mPFC to investigate the effects of adding the novel atypical antipsychotic drug asenapine to the SSRI escitalopram with regards to monoamine outflow in the mPFC and dopamine outflow in nucleus accumbens as well as glutamatergic transmission in the mPFC. Results: The present study shows that addition of low doses (0.05 and 0.1 mg/kg) of asenapine to escitalopram (5 mg/kg) markedly enhances dopamine, noradrenaline, and serotonin release in the rat mPFC as well as dopamine release in the nucleus accumbens. Moreover, this drug combination facilitated both N-methyl-d-Aspartate (NMDA)– and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–induced currents as well as electrically evoked excitatory postsynaptic potentials in pyramidal cells of the rat mPFC. Conclusions: Our results support the notion that the augmentation of SSRIs by atypical antipsychotic drugs in treatment-resistant depression may, at least in part, be related to enhanced catecholamine output in the prefrontal cortex and that asenapine may be clinically used to achieve this end. In particular, the subsequent activation of the D1 receptor may be of importance for the augmented antidepressant effect, as this mechanism facilitated both NMDA and AMPA receptor-mediated transmission in the mPFC. Our novel observation that the drug combination, like ketamine, facilitates glutamatergic transmission in the mPFC may contribute to explain the rapid and potent antidepressant

[Effect of tail-suspension on the reproduction of adult male rats].

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Zhou, Dang-xia; Qiu, Shu-dong; Wang, Zhi-yong; Zhang, Jie

2006-04-01

To study the effects on the male reproduction in adult male rats and its mechanisms through simulated weightlessness using tail-suspension, in order to do a basic works of exploring the effects on human being's reproduction in outer space. Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then we examined the weight and morphology of testis, the quality and amount of sperm, also tested the serum hormone by radioimmunoassay and analyzed apoptosis rate of testicular cells by TUNEL in the experimental rats and control rats. After tail-suspension, the weight of testis, the sperm count and sperm motility significantly decreased (P 0.05). These changes were not significant between two experimental groups (P > 0.05). In addition, the seminiferous tubules became atrophy with the reduction of the layers of seminiferous epithelium, and sperm amount in lumens of seminiferous tubules decreased in experimental groups. The above were more remarkable in the 28 d experimental group. Simulating weightlessness has a harmful effect on reproduction of adult male rats. These may be caused by inducing apoptosis. The blocking apoptosis of testicular cells may be useful in improving the harmful effect.

Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex.

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Sanna, Fabrizio; Bratzu, Jessica; Piludu, Maria A; Corda, Maria G; Melis, Maria R; Giorgi, Osvaldo; Argiolas, Antonio

2017-01-01

Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system.

Stress amplifies sex differences in primate prefrontal profiles of gene expression.

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Lee, Alex G; Hagenauer, Megan; Absher, Devin; Morrison, Kathleen E; Bale, Tracy L; Myers, Richard M; Watson, Stanley J; Akil, Huda; Schatzberg, Alan F; Lyons, David M

2017-11-02

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys. Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex. Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele.

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Xiaojing Ye

Full Text Available Insulin like growth factor 2 (Igf2 is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain.

Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

African Journals Online (AJOL)

Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

NARCIS (Netherlands)

Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

2004-01-01

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively

Comparison and modification of Pu-239 kinetics in young and adult rats

International Nuclear Information System (INIS)

Volf, V.; Gamer, A.; Laengle, U.

1987-01-01

It is obvious that the biokinetics of bone-seeking radionuclides are influenced by skeletal growth and remodelling, the rate of which in general decreases with increasing age. For plutonium, Mahlum and Sikov (1974) observed that rats injected with Pu-239 as weanlings retained a lower percentage in the liver and more in the bones than the animals injected as adults. However, skeletal Pu-239 was diluted more rapidly in the young rats because of intensive new bone formation and this led to a more pronounced reduction in the accumulation of radiation dose than was the case in adult animals. The aim of the present experiments was to study: a) The age effect on Pu-239 biokinetics in adult rates as influenced by the sex of the animals. b) Early retention and distribution of Pu-239 in the bones of young and adult rats injected with an optimal osteosarcomogenic dose. c) The effectiveness of a delayed prolonged administration of Zn-DTPA in drinking water for the mobilization of injected Pu-239 in rats of various age. 3 refs.; 5 figs.; 1 table

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

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Chaillan, F A; Marchetti, E; Delfosse, F; Roman, F S; Soumireu-Mourat, B

1997-01-01

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats.

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Abekawa, Tomohiro; Ito, Koki; Nakagawa, Shin; Koyama, Tsukasa

2007-06-01

Neurodevelopmental deficits of parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism.

Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

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Abdul-Rahman Omar

2012-02-01

Full Text Available Abstract Background There has been an increasing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Results Following pathway analysis and validation of gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1, CD47 (Cluster of Differentiation 47 and the RET (Rearranged During Transfection protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipid metabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus striatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. Conclusions According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes.

Prefrontal cerebral blood volume patterns while playing video games--a near-infrared spectroscopy study.

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Nagamitsu, Shinichiro; Nagano, Miki; Yamashita, Yushiro; Takashima, Sachio; Matsuishi, Toyojiro

2006-06-01

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

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Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-11-01

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Less Effort, Better Results: How Does Music Act on Prefrontal Cortex in Older Adults during Verbal Encoding? An fNIRS Study

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Ferreri, Laura; Bigand, Emmanuel; Perrey, Stephane; Muthalib, Makii; Bard, Patrick; Bugaiska, Aurélia

2014-01-01

Several neuroimaging studies of cognitive aging revealed deficits in episodic memory abilities as a result of prefrontal cortex (PFC) limitations. Improving episodic memory performance despite PFC deficits is thus a critical issue in aging research. Listening to music stimulates cognitive performance in several non-purely musical activities (e.g., language and memory). Thus, music could represent a rich and helpful source during verbal encoding and therefore help subsequent retrieval. Furthermore, such benefit could be reflected in less demand of PFC, which is known to be crucial for encoding processes. This study aimed to investigate whether music may improve episodic memory in older adults while decreasing the PFC activity. Sixteen healthy older adults (μ = 64.5 years) encoded lists of words presented with or without a musical background while their dorsolateral prefrontal cortex (DLPFC) activity was monitored using a eight-channel continuous-wave near-infrared spectroscopy (NIRS) system (Oxymon Mk III, Artinis, The Netherlands). Behavioral results indicated a better source-memory performance for words encoded with music compared to words encoded with silence (p music encoding condition compared to the silence condition (p music modulates the activity of the DLPFC during encoding in a less-demanding direction. Taken together, our results indicate that music can help older adults in memory performances by decreasing their PFC activity. These findings open new perspectives about music as tool for episodic memory rehabilitation on special populations with memory deficits due to frontal lobe damage such as Alzheimer’s patients. PMID:24860481

Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.

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Roth, Tania L; Zoladz, Phillip R; Sweatt, J David; Diamond, David M

2011-07-01

Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have been linked with memory, stress, and neuropsychiatric disorders. Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. Adult male Sprague-Dawley rats were given psychosocial stress composed of two acute cat exposures in conjunction with 31 days of daily social instability. These manipulations have been shown previously to produce physiological and behavioral sequelae in rats that are comparable to symptoms observed in traumatized people with PTSD. We then assessed Bdnf DNA methylation patterns (at exon IV) and gene expression. We have found here that the psychosocial stress regimen significantly increased Bdnf DNA methylation in the dorsal hippocampus, with the most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen significantly decreased methylation in the ventral hippocampus (CA3). No changes in Bdnf DNA methylation were detected in the medial prefrontal cortex or basolateral amygdala. In addition, there were decreased levels of Bdnf mRNA in both the dorsal and ventral CA1. These results provide evidence that traumatic stress occurring in adulthood can induce CNS gene methylation, and specifically, support the hypothesis that epigenetic marking of the Bdnf gene may underlie hippocampal dysfunction in response to traumatic stress. Furthermore, this work provides support for the speculative notion that altered hippocampal Bdnf DNA methylation is a cellular mechanism underlying the persistent cognitive deficits which are prominent features of the pathophysiology of PTSD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prefrontal cortex modulates desire and dread generated by nucleus accumbens glutamate disruption.

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Richard, Jocelyn M; Berridge, Kent C

2013-02-15

Corticolimbic circuits, including direct projections from prefrontal cortex to nucleus accumbens (NAc), permit top-down control of intense motivations generated by subcortical circuits. In rats, localized disruptions of glutamate signaling within medial shell of NAc generate desire or dread, anatomically organized along a rostrocaudal gradient analogous to a limbic keyboard. At rostral locations in shell, these disruptions generate appetitive eating, but at caudal locations the disruptions generate progressively fearful behaviors (distress vocalizations, escape attempts, and antipredator reactions). Here, we asked whether medial prefrontal cortex can modulate intense motivations generated by subcortical NAc disruptions. We used simultaneous microinjections in medial prefrontal cortex regions and in NAc shell to examine whether the desire or dread generated by NAc shell disruptions is modulated by activation/inhibition of three specific regions of prefrontal cortex: medial orbitofrontal cortex, infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the human), or prelimbic cortex (midventral anterior cingulate). We found that activation of medial orbitofrontal cortex biased intense bivalent motivation in an appetitive direction by amplifying generation of eating behavior by middle to caudal NAc disruptions, without altering fear. In contrast, activation of infralimbic prefrontal cortex powerfully and generally suppressed both appetitive eating and fearful behaviors generated by NAc shell disruptions. These results suggest that corticolimbic projections from discrete prefrontal regions can either bias motivational valence or generally suppress subcortically generated intense motivations of desire or fear. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Different Astrocytic Activation between Adult Gekko japonicus and Rats during Wound Healing In Vitro.

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Yun Gu

Full Text Available Glial scar formation is a major obstacle to regeneration after spinal cord injury. Moreover, it has been shown that the astrocytic response to injury differs between species. Gekko japonicas is a type of reptile and it shows differential glial activation compared to that of rats. The purpose of the present study was to compare the proliferation and migration of astrocytes in the spinal cords of geckos and rats after injury in vitro. Spinal cord homogenate stimulation and scratch wound models were used to induce astrocytic activation in adult and embryonic rats, as well as in adult geckos. Our results indicated that astrocytes from the adult rat were likely activated by mechanical stimulation, even though they showed lower proliferation abilities than the astrocytes from the gecko under normal conditions. Furthermore, a transcriptome analysis revealed that the differentially expressed genes in astrocytes from adult rats and those from geckos were enriched in pathways involved in proliferation and the response to stimuli. This implies that intrinsic discrepancies in gene expression patterns might contribute to the differential activation of astrocytes between species.

Functional compensation in the ventromedial prefrontal cortex improves memory-dependent decisions in older adults.

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Lighthall, Nichole R; Huettel, Scott A; Cabeza, Roberto

2014-11-19

Everyday consumer choices frequently involve memory, as when we retrieve information about consumer products when making purchasing decisions. In this context, poor memory may affect decision quality, particularly in individuals with memory decline, such as older adults. However, age differences in choice behavior may be reduced if older adults can recruit additional neural resources that support task performance. Although such functional compensation is well documented in other cognitive domains, it is presently unclear whether it can support memory-guided decision making and, if so, which brain regions play a role in compensation. The current study engaged younger and older humans in a memory-dependent choice task in which pairs of consumer products from a popular online-shopping site were evaluated with different delays between the first and second product. Using functional imaging (fMRI), we found that the ventromedial prefrontal cortex (vmPFC) supports compensation as defined by three a priori criteria: (1) increased vmPFC activation was observed in older versus younger adults; (2) age-related increases in vmPFC activity were associated with increased retrieval demands; and (3) increased vmPFC activity was positively associated with performance in older adults-evidence of successful compensation. Extending these results, we observed evidence for compensation in connectivity between vmPFC and the dorsolateral PFC during memory-dependent choice. In contrast, we found no evidence for age differences in value-related processing or age-related compensation for choices without delayed retrieval. Together, these results converge on the conclusion that age-related decline in memory-dependent choice performance can be minimized via functional compensation in vmPFC. Copyright © 2014 the authors 0270-6474/14/3415648-10$15.00/0.

The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

Science.gov (United States)

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

2014-07-01

The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

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Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-07-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

khat distorts the prefrontal cortex histology and function of adult

African Journals Online (AJOL)

2018-02-28

Feb 28, 2018 ... It affects many brain centers including the prefrontal cortex which is the ... cognitive behaviors however; it is linked to many psychological ... by traumatic events while others experience ... scientific research in exposing the effects. ... between 3 to 5pm daily. ... needle attached a plastic tubing was connected.

Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

Science.gov (United States)

Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

2004-01-01

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats

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Andino-Pavlovsky, Victoria; Souza, Annie C.; Scheffer-Teixeira, Robson; Tort, Adriano B. L.; Etchenique, Roberto; Ribeiro, Sidarta

2017-01-01

Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC. PMID:28536507

Interaction between the medial prefrontal cortex and hippocampal CA1 area is essential for episodic-like memory in rats.

Science.gov (United States)

Chao, Owen Y; Nikolaus, Susanne; Lira Brandão, Marcus; Huston, Joseph P; de Souza Silva, Maria A

2017-05-01

The interplay between medial prefrontal cortex (mPFC) and hippocampus, particularly the hippocampal CA3 area, is critical for episodic memory. To what extent the mPFC also interacts with the hippocampus CA1 subregion still requires elucidation. To investigate this issue, male rats received unilateral N-methyl- D -aspartate lesions of the mPFC together with unilateral lesions of the hippocampal CA1 area, either in the same (control) or in the opposite hemispheres (disconnection). They underwent an episodic-like memory test, combining what-where-when information, and separate tests for novel object preference (what), object place preference (where) and temporal order memory (when). Compared to controls, the disconnected mPFC-CA1 rats exhibited disrupted episodic-like memory with an impaired integration of the what-where-when elements. Both groups showed intact memories for what and when, while only the control group showed intact memory for where. These findings suggest that the functional interaction of the mPFC-CA1 circuit is crucial for the processing of episodic memory and, in particular, for the integration of the spatial memory component. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroanatomical Substrates of Executive Functions: Beyond Prefrontal Structures

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Bettcher, Brianne M.; Mungas, Dan; Patel, Nihar; Elofson, Jonathan; Dutt, Shubir; Wynn, Matthew; Watson, Christa L.; Stephens, Melanie; Walsh, Christine M.; Kramer, Joel H.

2016-01-01

Executive functions are often considered lynchpin “frontal lobe tasks”, despite accumulating evidence that a broad network of anterior and posterior brain structures supports them. Using a latent variable modeling approach, we assessed whether prefrontal grey matter volumes independently predict executive function performance when statistically differentiated from global atrophy and individual non-frontal lobar volume contributions. We further examined whether fronto-parietal white matter microstructure underlies and independently contributes to executive functions. We developed a latent variable model to decompose lobar grey matter volumes into a global grey matter factor and specific lobar volumes (i.e. prefrontal, parietal, temporal, occipital) that were independent of global grey matter. We then added mean fractional anisotropy (FA) for the superior longitudinal fasciculus (dorsal portion), corpus callosum, and cingulum bundle (dorsal portion) to models that included grey matter volumes related to cognitive variables in previous analyses. Results suggested that the 2-factor model (shifting/inhibition, updating/working memory) plus an information processing speed factor best explained our executive function data in a sample of 202 community dwelling older adults, and was selected as the base measurement model for further analyses. Global grey matter was related to the executive function and speed variables in all four lobar models, but independent contributions of the frontal lobes were not significant. In contrast, when assessing the effect of white matter microstructure, cingulum FA made significant independent contributions to all three executive function and speed variables and corpus callosum FA was independently related to shifting/inhibition and speed. Findings from the current study indicate that while prefrontal grey matter volumes are significantly associated with cognitive neuroscience measures of shifting/inhibition and working memory in healthy

Dietary modulation of parathion-induced neurotoxicity in adult and juvenile rats.

Science.gov (United States)

Liu, Jing; Karanth, Subramanya; Pope, Carey

2005-06-01

Previous studies indicated that dietary glucose (15% in drinking water) could markedly exacerbate the toxicity of parathion in adult rats. The present study evaluated the effect of consumption of the commonly used sweetener, high fructose corn syrup (HFCS), on parathion toxicity in adult and juvenile rats. Animals were given free access to either water or 15% HFCS in drinking water for a total of 10 days and challenged with parathion (6 or 18 mg/kg, s.c., for juveniles or adults, respectively) on the 4th day. Signs of cholinergic toxicity, body weight and chow/fluid intake were recorded daily. Acetylcholinesterase (AChE) activity and immunoreactivity (AChE-IR) in frontal cortex and diaphragm were measured at 2, 4, and 7 days after parathion. As HFCS was associated with significant reduction in chow intake, adult rats were also pair-fed to evaluate the effect of similar reduced chow intake alone on parathion toxicity. The results indicated that the cholinergic toxicity of parathion was significantly increased by HFCS feeding in both age groups. The excess sugar consumption, however, did not significantly affect parathion-induced AChE inhibition in either tissue or either age group. Enzyme immunoreactivity in frontal cortex was generally not affected in either age group while diaphragm AChE-IR was significantly reduced by parathion and HFCS alone in adult animals at 2 and 4 days timepoints, and more so by the combination of sugar feeding and parathion exposure in both age groups. Food restriction alone did not exacerbate parathion toxicity. While the mechanism(s) remains unclear, we conclude that voluntary consumption of the common sweetener HFCS can markedly amplify parathion acute toxicity in both juvenile and adult rats.

Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

Science.gov (United States)

González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

2016-02-01

The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex.

Science.gov (United States)

MacDowell, Karina S; Sayd, Aline; García-Bueno, Borja; Caso, Javier R; Madrigal, José L M; Leza, Juan Carlos

2017-09-01

Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.

Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

OpenAIRE

Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

2008-01-01

The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors

Science.gov (United States)

Ceglia, I; Acconcia, S; Fracasso, C; Colovic, M; Caccia, S; Invernizzi, R W

2004-01-01

Microdialysis was used to study the acute and chronic effects of escitalopram (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5-hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. Extracellular 5-HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of 0.15 and 0.63 mg kg−1 ESCIT. No further increase was observed at 2.5 mg kg−1 ESCIT (290%). The effect of 13-day s.c. infusion of 10 mg kg−1day−1 ESCIT on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of baseline), whereas exposure to ESCIT was similar. In contrast, the increase in extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%) was similar. However, brain and plasma levels of S-citalopram in rats infused with CIT for 13 days were lower than after 2 days. Acute treatment with 2.5 mg kg−1 ESCIT or 5 mg kg−1 CIT raised extracellular 5-HT by 243 and 276%, respectively, in rats given chronic vehicle but had no effect in rats given ESCIT (10 mg kg−1 day−1) or CIT (20 mg kg−1 day−1) for 2 or 13 days, suggesting that the infused doses had maximally increased extracellular 5-HT. WAY100,635 (0.1 mg kg−1 s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days, respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164% of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days, respectively. 8-OH-DPAT (0.025 mg kg−1) reduced extracellular 5-HT by 54% in control rats, but had no effect in those given ESCIT and CIT for 13 days. This series of experiments led to the conclusion that chronic treatment with ESCIT desensitizes the 5-HT1A

Assessing competence of broccoli consumption on inflammatory and antioxidant pathways in restraint-induced models: estimation in rat hippocampus and prefrontal cortex.

Science.gov (United States)

Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Sarraf Zadeh, Sadaf; Pour, Marieh Hossein; Ashabi, Ghorbangol; Khodagholi, Fariba; Ahmadiani, Abolhassan

2013-01-01

A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA) level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

Assessing Competence of Broccoli Consumption on Inflammatory and Antioxidant Pathways in Restraint-Induced Models: Estimation in Rat Hippocampus and Prefrontal Cortex

Directory of Open Access Journals (Sweden)

Leila Khalaj

2013-01-01

Full Text Available A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2 antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

Long-term organ culture of adult rat colon

DEFF Research Database (Denmark)

Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

1978-01-01

. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

Changes caused by haloperidol are blocked by music in Wistar rat.

Science.gov (United States)

Tasset, Inmaculada; Quero, Ismael; García-Mayórgaz, Ángel D; del Río, Manuel Causse; Túnez, Isaac; Montilla, Pedro

2012-06-01

This study sought to evaluate the effect of classical music, using Mozart's sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were divided into four groups: (1) control, (2) haloperidol treatment (single dose of 2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a fall in plasma PRL and corticosterone levels in healthy rats (P music was associated with a significant increase in DA levels in all groups, with the increase being particularly marked in PFC and SN (P music, by contrast, enhances DA activity and turnover in the brain. The results obtained here bear out reports that music triggers a reduction in systolic pressure and an increase in mesencephalon dopamine levels in human and rats treated with ecstasy, through a calmodulin-dependent system.

Adrenal-dependent and -independent stress-induced Per1 mRNA in hypothalamic paraventricular nucleus and prefrontal cortex of male and female rats.

Science.gov (United States)

Chun, Lauren E; Christensen, Jenny; Woodruff, Elizabeth R; Morton, Sarah J; Hinds, Laura R; Spencer, Robert L

2018-01-01

Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extra-SCN brain regions. These extra-SCN molecular clocks depend on the SCN for entrainment to a light:dark cycle. The SCN has limited neural efferents, so it may entrain extra-SCN molecular clocks through its well-established circadian control of glucocorticoid hormone secretion. Glucocorticoids can regulate the normal rhythmic expression of clock genes in some extra-SCN tissues. Untimely stress-induced glucocorticoid secretion may compromise extra-SCN molecular clock function. We examined whether acute restraint stress during the rat's inactive phase can rapidly (within 30 min) alter clock gene (Per1, Per2, Bmal1) and cFos mRNA (in situ hybridization) in the SCN, hypothalamic paraventricular nucleus (PVN), and prefrontal cortex (PFC) of male and female rats (6 rats per treatment group). Restraint stress increased Per1 and cFos mRNA in the PVN and PFC of both sexes. Stress also increased cFos mRNA in the SCN of male rats, but not when subsequently tested during their active phase. We also examined in male rats whether endogenous glucocorticoids are necessary for stress-induced Per1 mRNA (6-7 rats per treatment group). Adrenalectomy attenuated stress-induced Per1 mRNA in the PVN and ventral orbital cortex, but not in the medial PFC. These data indicate that increased Per1 mRNA may be a means by which extra-SCN molecular clocks adapt to environmental stimuli (e.g. stress), and in the PFC this effect is largely independent of glucocorticoids.

Less Effort, Better Results: How Does Music Act on Prefrontal Cortex in Older Adults during Verbal Encoding? An fNIRS Study.

Science.gov (United States)

Ferreri, Laura; Bigand, Emmanuel; Perrey, Stephane; Muthalib, Makii; Bard, Patrick; Bugaiska, Aurélia

2014-01-01

Several neuroimaging studies of cognitive aging revealed deficits in episodic memory abilities as a result of prefrontal cortex (PFC) limitations. Improving episodic memory performance despite PFC deficits is thus a critical issue in aging research. Listening to music stimulates cognitive performance in several non-purely musical activities (e.g., language and memory). Thus, music could represent a rich and helpful source during verbal encoding and therefore help subsequent retrieval. Furthermore, such benefit could be reflected in less demand of PFC, which is known to be crucial for encoding processes. This study aimed to investigate whether music may improve episodic memory in older adults while decreasing the PFC activity. Sixteen healthy older adults (μ = 64.5 years) encoded lists of words presented with or without a musical background while their dorsolateral prefrontal cortex (DLPFC) activity was monitored using a eight-channel continuous-wave near-infrared spectroscopy (NIRS) system (Oxymon Mk III, Artinis, The Netherlands). Behavioral results indicated a better source-memory performance for words encoded with music compared to words encoded with silence (p < 0.05). Functional NIRS data revealed bilateral decrease of oxyhemoglobin values in the music encoding condition compared to the silence condition (p < 0.05), suggesting that music modulates the activity of the DLPFC during encoding in a less-demanding direction. Taken together, our results indicate that music can help older adults in memory performances by decreasing their PFC activity. These findings open new perspectives about music as tool for episodic memory rehabilitation on special populations with memory deficits due to frontal lobe damage such as Alzheimer's patients.

Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

Directory of Open Access Journals (Sweden)

Sanchez-Criado Jose E

2004-09-01

Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

Directory of Open Access Journals (Sweden)

Matthias eKlugmann

2011-07-01

Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

Science.gov (United States)

Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

2006-09-01

Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

No significant effect of prefrontal tDCS on working memory performance in older adults

Directory of Open Access Journals (Sweden)

Jonna eNilsson

2015-12-01

Full Text Available Transcranial direct current stimulation (tDCS has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1mA and 2mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment

NARCIS (Netherlands)

van Harmelen, A.L.; van Tol, M.J.; Dalgleish, T.; van der Wee, N.J.A.; Veltman, D.J.; Aleman, A.; Spinhoven, P.; Penninx, B.W.J.H.; Elzinga, B.M.

2014-01-01

Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional

Some behavioral aspects of adult rats irradiated prenatally

International Nuclear Information System (INIS)

Vekovishcheva, O.Yu.; Blagova, O.E.; Borovitskaya, A.E.; Evtushenko, V.I.; Khanson, K.P.

1992-01-01

This is a study of the effects of prenatal irradiation on the behavior of rats. The experiments were performed on 42 eighteen month old rats of both sexes. Eight of the males and thirteen females had been irradiated prenatally. The results of this experiment indicated that in general, the activation of behavior, the appearance of aggression and the increase in chaos along with the presence of behavior poses were typical of the suppressed condition of the prenatal irradiated animal. Also, among prenatally irradiated animals, there was a greater degree of anxiety, a slow rate of adjustment to unfamiliar situations and unfriendly relationships between animals of the same sex. These results were compared with the results of behavioral experiments on irradiated adult rats

Chronic Stress Impairs Prefrontal Cortex-Dependent Response Inhibition and Spatial Working Memory

Science.gov (United States)

Mika, Agnieszka; Mazur, Gabriel J.; Hoffman, Ann N.; Talboom, Joshua S.; Bimonte-Nelson, Heather A.; Sanabria, Federico; Conrad, Cheryl D.

2012-01-01

Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

Science.gov (United States)

Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

2017-02-01

Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

Science.gov (United States)

Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

2015-01-01

The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation.

Science.gov (United States)

McLean, Samantha L; Harte, Michael K; Neill, Joanna C; Young, Andrew Mj

2017-06-01

Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

Science.gov (United States)

Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.

Science.gov (United States)

Cardoso-Cruz, Helder; Sousa, Mafalda; Vieira, Joana B; Lima, Deolinda; Galhardo, Vasco

2013-11-01

The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

EFFECTS OF EARLY POSTNATAL ANOXIA ON ADULT LEARNING AND EMOTION IN RATS

NARCIS (Netherlands)

BUWALDA, B; NYAKAS, C; VOSSELMAN, HJ; LUITEN, PGM; Vosselman, Henk Jan

Cognitive functioning, behavioural attention and anxiety were studied in adult male Wistar rats after early postnatal anoxia. Spatial memory performance in the holeboard learning task was impaired in anoxic rats when compared with control animals. Attention assessed by the behavioural immobility

Turnover time of Leydig cells and other interstitial cells in testes of adult rats

NARCIS (Netherlands)

Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

1989-01-01

The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

Science.gov (United States)

Fan, Chunling; Zhang, Mengqi; Shang, Lei; Cynthia, Ngobe Akume; Li, Zhi; Yang, Zhenyu; Chen, Dan; Huang, Jufang; Xiong, Kun

2014-01-01

Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs. PMID:25206818

Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

OpenAIRE

Auger, Meagan L.; Floresco, Stan B.

2014-01-01

Background: Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. Methods: We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates ...

Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior and Neuronal Morphology in the Prefrontal Cortex and Hippocampus.

Science.gov (United States)

de Melo, Silvana Regina; de David Antoniazzi, Caren Tatiane; Hossain, Shakhawat; Kolb, Bryan

2018-01-01

The long-lasting effects of early stress on brain development have been well studied. Recent evidence indicates that males and females respond differently to the same stressor. We examined the chronic effects of daily maternal separation (MS) on behavior and cerebral morphology in both male and female rats. Cognitive and anxiety-like behaviors were evaluated, and neuroplastic changes in 2 subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in adult male and female rats. The animals were subjected to MS on postnatal day (P) 3-14 for 3 h per day. Cognitive and emotional behaviors were assessed in the object/context mismatch task, elevated plus maze, and locomotor activity test in early adulthood (P87-P95). Anatomical assessments were performed in the prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety-related behavior only in males, whereas locomotor activity was higher in females, with no effects on cognition. MS decreased spine density in the AID and increased spine density in the CA1 area in males. Females exhibited an increase in spine density in the Cg3. Our findings confirm previous work that found that MS causes long-term behavioral and anatomical effects, and these effects were dependent on sex and the duration of MS stress. © 2018 S. Karger AG, Basel.

Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

Directory of Open Access Journals (Sweden)

Hadley C Bergstrom

2015-12-01

Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

Sex specific recruitment of a medial prefrontal cortex-hippocampal-thalamic system during context-dependent renewal of responding to food cues in rats.

Science.gov (United States)

Anderson, Lauren C; Petrovich, Gorica D

2017-03-01

Renewal, or reinstatement, of responding to food cues after extinction may explain the inability to resist palatable foods and change maladaptive eating habits. Previously, we found sex differences in context-dependent renewal of extinguished Pavlovian conditioned responding to food cues. Context-induced renewal involves cue-food conditioning and extinction in different contexts and the renewal of conditioned behavior is induced by return to the conditioning context (ABA renewal). Male rats showed renewal of responding while females did not. In the current study we sought to identify recruitment of key neural systems underlying context-mediated renewal and sex differences. We examined Fos induction within the ventromedial prefrontal cortex (vmPFC), hippocampal formation, thalamus and amygdala in male and female rats during the test for renewal. We found sex differences in vmPFC recruitment during renewal. Male rats in the experimental condition showed renewal of responding and had more Fos induction within the infralimbic and prelimbic vmPFC areas compared to controls that remained in the same context throughout training and testing. Females in the experimental condition did not show renewal or an increase in Fos induction. Additionally, Fos expression differed between experimental and control groups and between the sexes in the hippocampal formation, thalamus and amygdala. Within the ventral subiculum, the experimental groups of both sexes had more Fos compared to control groups. Within the dorsal CA1 and the anterior region of the paraventricular nucleus of the thalamus, in males, the experimental group had higher Fos induction, while both females groups had similar number of Fos-positive neurons. Within the capsular part of the central amygdalar nucleus, females in the experimental group had higher Fos induction, while males groups had similar amounts. The differential recruitment corresponded to the behavioral differences between males and females and suggests

The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

Czech Academy of Sciences Publication Activity Database

Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

2017-01-01

Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

Effect of Consuming Iodized Salt on Fertility Indices in Male Adult Rats

Directory of Open Access Journals (Sweden)

M. Mehrabani Natanzi

2017-06-01

Full Text Available Introduction: Today about 27.4 percent of female 15-44 years and 1 percent of female in fertility age are affected by infertility. Iodine is a rare element that is essential for the synthesis of thyroid hormones. Concentration of the thyroid hormones in blood under the influence of iodine intake and changes in thyroid hormones levels interact with reproductive system. Today, all the people of Iran consuming iodized salt regardless of iodine status in their body. In this study according to high prevalence of the infertility among young couples, iodized salt intake on fertility in male rats were investigated. Materials and Methods: In this study 20 male and 20 female adult Wistar rats were used. Twenty male adult Wistar rats were randomly divided into 2 groups. Including the control group and treatment group that received iodine and female adult Wistar were fed with a regular diet. Five male rats from each group were killed at the end of the fourth weeks in order to evaluate the possible effect of iodized salt on sperm analysis and weight of testis. After a month, male and female rats were placed in pairs in separate cages and their offspring were investigated in terms of number, gender and health. Results: The result of this study showed that the number of healthy offspring of treated male rats was significantly lower than the control group. Conclusion: Due to the negative effect of excessive iodine intake on fertility rate, it is recommended to couples to perform functional tests of their thyroid glands before intake of iodized salts.

A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

Science.gov (United States)

Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

2014-04-10

In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.

Science.gov (United States)

Madsen, Heather B; Zbukvic, Isabel C; Luikinga, Sophia J; Lawrence, Andrew J; Kim, Jee Hyun

2017-09-01

Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high. Copyright © 2016 Elsevier Inc. All rights reserved.

Prefrontal serotonin transporter availability is positively associated with the cortisol awakening response

DEFF Research Database (Denmark)

Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

2013-01-01

higher cortisol responses when exposed to psychosocial stressors relative to high expressing 5-HTTLPR variants. However, it is not clear how the relation between SERT and cortisol output is reflected in the adult brain. We investigated the relation between cortisol response to awakening (CAR) and SERT...... binding in brain regions considered relevant to modify the cortisol awakening response. Methods: thirty-two healthy volunteers underwent in vivo SERT imaging with [11C]DASB-Positron Emission Tomography (PET), genotyping, and performed home-sampling of saliva to assess CAR. Results: CAR, defined...... between CAR and prefrontal SERT binding as tested by an interaction analysis (genotype×CAR). Conclusion: prefrontal SERT binding is positively associated with cortisol response to awakening. We speculate that in mentally healthy individuals prefrontal serotonergic neurotransmission may exert an inhibitory...

Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

Science.gov (United States)

Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

2012-08-01

Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

Science.gov (United States)

Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

2010-03-01

Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

Science.gov (United States)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

Histological changes in the cerebelli of adult wistar rats exposed to ...

African Journals Online (AJOL)

The different constituents of tobacco smoke have been linked to different diseased conditions. In this work, the histological effects of cigarette smoke on the cerebellum of adult male Wistar rats were studied. Sixteen Wistar rats with mean weight of 153.24 ± 4.12 g were grouped equally into four. The Control Group A was ...

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

Science.gov (United States)

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Modification Of Cesium Toxicity By Prussian Blue In Adult Male Albino Rats

International Nuclear Information System (INIS)

MANGOOD, S.A.; HAGGAG, A.M.

2009-01-01

The purposes of this study were to asses the toxicological effects of stable cesium chloride, and investigate the possible therapeutic role of Prussian blue (PB) in adult male albino rats.Thirty two adult male albino rats were used in this study and classified to 4 groups (8 rats/group) as follows:1- Group one (G1): rats were considered as controls and kept on the commercial diet without any treatments.2-Group two (G2): treated with daily oral cesium chloride (50 mg/300 g body weight).3-Group three (G3): treated with daily oral Prussian blue (250 mg/rats).4-Group four (G4): treated with cesium chloride at a daily oral dose of 50 mg/300 g body weight + Prussian blue at a daily oral dose of 250 mg/rats.All animals were administered the CsCl and/or PB via intubation tube and the duration of this study was 35 consecutive days. Hemoglobin (Hb), hematocrit (Ht%), red blood cells (RBC), white blood cells (WBC), folic acid, vitamin B12, total protein, albumin, globulin, A/G ratio, ALT, AST, total bilirubin, alkaline phosphatase, blood glucose, urea, creatinine, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), sodium, potassium, calcium and inorganic phosphorous and body weight were determined in all groups.The data obtained revealed that the intake of stable cesium chloride in adult male rats caused significant decreases in the Hb, hematocrit, folic acid, vitamin B12 and potassium contents, with significant increases in WBC count, urea and creatinine levels and no effect on the other parameters. On the other hand, PB as a therapeutic agent caused significant amelioration in the changes produced by CsCl with variable degrees leading to the conclusion that the therapeutic agents might provide a protection against the toxicological effects of CsCl.

Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood

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Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

2015-01-01

Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period. PMID:26617490

Synaptic impairment in layer 1 of the prefrontal cortex induced by repeated stress during adolescence is reversed in adulthood

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Ignacio eNegron-Oyarzo

2015-11-01

Full Text Available Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC. There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory postsynaptic potential (fEPSP in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in AMPA/kainate receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD. Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period.

Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

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Prince Gregory A

2009-06-01

Full Text Available Abstract Background Increased respiratory rate (tachypnea is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection. Methods Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old and adult (6–12 week old cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph. Results Adult cotton rats had significantly greater tidal volume (TV, and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals. Conclusion While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume is

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Directory of Open Access Journals (Sweden)

A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

An exploratory study of the effects of spatial working-memory load on prefrontal activation in low- and high-performing elderly.

Science.gov (United States)

Vermeij, Anouk; van Beek, Arenda H E A; Reijs, Babette L R; Claassen, Jurgen A H R; Kessels, Roy P C

2014-01-01

Older adults show more bilateral prefrontal activation during cognitive performance than younger adults, who typically show unilateral activation. This over-recruitment has been interpreted as compensation for declining structure and function of the brain. Here we examined how the relationship between behavioral performance and prefrontal activation is modulated by different levels of working-memory load. Eighteen healthy older adults (70.8 ± 5.0 years; MMSE 29.3 ± 0.9) performed a spatial working-memory task (n-back). Oxygenated ([O2Hb]) and deoxygenated ([HHb]) hemoglobin concentration changes were registered by two functional Near-Infrared Spectroscopy (fNIRS) channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition. [O2Hb] increased with rising working-memory load in both fNIRS channels. Based on the performance in the high working-memory load condition, the group was divided into low and high performers. A significant interaction effect of performance level and hemisphere on [O2Hb] increase was found, indicating that high performers were better able to keep the right prefrontal cortex engaged under high cognitive demand. Furthermore, in the low performers group, individuals with a larger decline in task performance from the control to the high working-memory load condition had a larger bilateral increase of [O2Hb]. The high performers did not show a correlation between performance decline and working-memory load related prefrontal activation changes. Thus, additional bilateral prefrontal activation in low performers did not necessarily result in better cognitive performance. Our study showed that bilateral prefrontal activation may not always be successfully compensatory. Individual behavioral performance should be taken into account to be able to distinguish successful and unsuccessful compensation or declined neural efficiency.

Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

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MacPhail, R C; Farmer, J D; Jarema, K A

2012-01-01

Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

Gastrointestinal absorption and retention of polonium in adult and newborn rats and guinea pigs

International Nuclear Information System (INIS)

Haines, J.W.; Naylor, G.P.L.; Pottinger, H.; Harrison, J.D.

1993-01-01

The gastrointestinal absorption of 210 Po was determined by comparing tissue retention after oral and systemic administration. The results indicate an increase in absorption in adult rats for 210 Po administered in liver compared with 210 Po nitrate with estimated absorption of 5 and 13%, respectively. For 210 Po citrate, values of about 7% were obtained in 1-day-old neonate and adult rats while absorption in guinea pigs was estimated to be about 23% in 1-day-old neonates, 17% in 5-day-old neonates, and 9% in adults. Gut retention of ingested 210 Po in neonates was high in rats but not guinea pigs. In adult animals, but not neonates, the liver accounted for a greater proportion of 210 Po reaching the bloodstream after ingestion than after systemic injection. The significance of these results is discussed in relation to current assumptions made in the calculation of doses from 210 Po. (author)

Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

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Zhen Feng

2015-01-01

Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

Development of Rostral Prefrontal Cortex and Cognitive and Behavioural Disorders

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Dumontheil, Iroise; Burgess, Paul W.; Blakemore, Sarah-Jayne

2008-01-01

Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in…

Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

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Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

2011-07-01

Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

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Romana Šlamberová

2014-01-01

Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

Science.gov (United States)

Wilson, C. Brad; Ebenezer, Philip J.; McLaughlin, Leslie D.; Francis, Joseph

2014-01-01

Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a

Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex.

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C Brad Wilson

Full Text Available Post-Traumatic Stress Disorder (PTSD can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC. Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE, 5-Hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA, dopamine (DA, and 3,4-Dihydroxyphenylacetic acid (DOPAC, and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC. In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may

Social instability stress differentially affects amygdalar neuron adaptations and memory performance in adolescent and adult rats

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Sheng-Feng eTsai

2014-02-01

Full Text Available Adolescence is a time of developmental changes and reorganization in the brain. It has been hypothesized that stress has a greater neurological impact on adolescents than on adults. However, scientific evidence in support of this hypothesis is still limited. We treated adolescent (4-week-old and adult (8-week-old rats with social instability stress for five weeks and compared the subsequent structural and functional changes to amygdala neurons. In the stress-free control condition, the adolescent group showed higher fear-potentiated startle responses, larger dendritic arborization, more proximal dendritic spine distribution and lower levels of truncated TrkB than the adult rats. Social instability stress exerted opposite effects on fear-potentiated startle responses in these two groups, i.e., the stress period appeared to hamper the performance in adolescents but improved it in adult rats. Furthermore, whilst the chronic social stress applied to adolescent rats reduced their dendritic field and spine density in basal and lateral amygdala neurons, the opposite stress effects on neuron morphology were observed in the adult rats. Moreover, stress in adolescence suppressed the amygdala expression of synaptic proteins, i.e., full-length TrkB and SNAP-25, whereas, in the adult rats, chronic stress enhanced full-length and truncated TrkB expressions in the amygdala. In summary, chronic social instability stress hinders amygdala neuron development in the adolescent brain, while mature neurons in the amygdala are capable of adapting to the stress. The stress induced age-dependent effects on the fear-potentiated memory may occur by altering the BDNF-TrkB signaling and neuroplasticity in the amygdala.

Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

DEFF Research Database (Denmark)

McCarthy, K J; Couchman, J R

1990-01-01

Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

Age- and Sex-Dependent Impact of Repeated Social Stress on Intrinsic and Synaptic Excitability of the Rat Prefrontal Cortex.

Science.gov (United States)

Urban, Kimberly R; Valentino, Rita J

2017-01-01

Stress is implicated in psychiatric illnesses that are characterized by impairments in cognitive functions that are mediated by the medial prefrontal cortex (mPFC). Because sex and age determine stress vulnerability, the effects of repeated social stress occurring during early adolescence, mid-adolescence, or adulthood on the cellular properties of male and female rat mPFC Layer V neurons in vitro were examined. Repeated resident-intruder stress produced age- and sex-specific effects on mPFC intrinsic and synaptic excitability. Mid-adolescents were particularly vulnerable to effects on intrinsic excitability. The maximum number of action potentials (APs) evoked by increasing current intensity was robustly decreased in stressed male and female mid-adolescent rats compared with age-matched controls. These effects were associated with stress-induced changes in AP half-width, amplitude, threshold, and input resistance. Social stress at all ages generally decreased synaptic excitability by decreasing the amplitude of spontaneous excitatory postsynaptic potentials. The results suggest that whereas social stress throughout life can diminish the influence of afferents driving the mPFC, social stress during mid-adolescence additionally affects intrinsic characteristics of mPFC neurons that determine excitability. The depressant effects of social stress on intrinsic and synaptic mPFC neurons may underlie its ability to affect executive functions and emotional responses, particularly during adolescence. © The Author 2016. Published by Oxford University Press.

Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

International Nuclear Information System (INIS)

Norton, S.

1986-01-01

Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation

Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

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John Paul Christianson

2014-10-01

Full Text Available Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed behavioral immunization. Recent data implicate neuroplasticity within the ventromedial prefrontal cortex (mPFC as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and one week later to uncontrollable tailshocks, followed 24h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDAR and the extracellular signal-regulated kinase (ERK cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL or infralimbic (IL mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent plasticity within the PL region is required for behavioral immunization, a learned form of stressor resistance.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

Science.gov (United States)

Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

Institute of Scientific and Technical Information of China (English)

Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

2009-01-01

BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P＜0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P＜0.05). CONCLUSION: Superior cervical ganglionectomy

Specialized prefrontal auditory fields: organization of primate prefrontal-temporal pathways

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Maria eMedalla

2014-04-01

Full Text Available No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal auditory field as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices.

Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

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Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

2013-08-01

Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

Copolymer-1 enhances cognitive performance in young adult rats

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Meneses, Alfredo; Cruz-Martínez, Yolanda; Anaya-Jiménez, Rosa María; Liy-Salmerón, Gustavo; Carvajal, Horacio Guillermo; Ponce-López, Maria Teresa

2018-01-01

Cognitive impairment is a dysfunction observed as a sequel of various neurodegenerative diseases, as well as a concomitant element in the elderly stages of life. In clinical settings, this malfunction is identified as mild cognitive impairment. Previous studies have suggested that cognitive impairment could be the result of a reduction in the expression of brain-derived neurotrophic factor (BDNF) and/or immune dysfunction. Copolymer-1 (Cop-1) is an FDA-approved synthetic peptide capable of inducing the activation of Th2/3 cells, which are able to release BDNF, as well as to migrate and accumulate in the brain. In this study, we evaluated the effect of Cop-1 immunization on improvement of cognition in adult rats. For this purpose, we performed four experiments. We evaluated the effect of Cop-1 immunization on learning/memory using the Morris water maze for spatial memory and autoshaping for associative memory in 3- or 6-month-old rats. BDNF concentrations at the hippocampus were determined by ELISA. Cop-1 immunization induced a significant improvement of spatial memory and associative memory in 6-month-old rats. Likewise, Cop-1 improved spatial memory and associative memory when animals were immunized at 3 months and evaluated at 6 months old. Additionally, Cop-1 induced a significant increase in BDNF levels at the hippocampus. To our knowledge, the present investigation reports the first instance of Cop-1 treatment enhancing cognitive function in normal young adult rats, suggesting that Cop-1 may be a practical therapeutic strategy potentially useful for age- or disease-related cognitive impairment. PMID:29494605

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

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Tania Rinaldi

2008-10-01

Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

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Laura Dazzi

Full Text Available Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1

Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

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Dazzi, Laura; Talani, Giuseppe; Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

2014-01-01

Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this

Self-generation and positivity effects following transcranial random noise stimulation in medial prefrontal cortex: A reality monitoring task in older adults.

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Mammarella, Nicola; Di Domenico, Alberto; Palumbo, Rocco; Fairfield, Beth

2017-06-01

Activation of medial Prefrontal Cortex (mPFC) has been typically found during reality monitoring tasks (i.e., distinguishing between internal self-generated vs external information). No study, however, has yet investigated whether transcranial Random Noise Stimulation (tRNS) over the mPFC leads to a reduction in reality-monitoring misattributions in aging. In particular, stimulating mPFC should increase the number of cognitive operations engaged while encoding and this distinctive information may help older adults to discriminate between internal and external sources better. In addition, given that older adults are more sensitive to positively-charged information compared to younger adults and that mPFC is typically recruited during encoding of positive stimuli with reference to themselves, activation of mPFC should further sustain source retrieval in older adults. In this double-blind, sham-controlled study, we examined whether tRNS over the mPFC of healthy younger and older adults during encoding enhances subsequent reality monitoring for seen versus imagined emotionally-charged words. Our findings show that tRNS enhances reality monitoring for positively-charged imagined words in the older adult group alone, highlighting the role that mPFC plays in their memory for positive information. In line with the control-based account of positivity effects, our results add evidence about the neurocognitive processes involved in reality monitoring when older adults face emotionally-charged events. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

International Nuclear Information System (INIS)

Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

2008-01-01

Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain

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Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory

2009-01-01

Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

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Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

Tooth movement characteristics in relation to root resorption in young and adult rats.

NARCIS (Netherlands)

Ren, Y.; Maltha, J.C.; Kuijpers-Jagtman, A.M.

2007-01-01

The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially.

Tooth movement characteristics in relation to root resorption in young and adult rats

NARCIS (Netherlands)

Ren, Yijin; Maltha, Jaap C.; Kuijpers-Jagtman, Anne Marie

2007-01-01

The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially.

Behavioral effects of nicotinic antagonist mecamylamine in a rat model of depression: prefrontal cortex level of BDNF protein and monoaminergic neurotransmitters.

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Aboul-Fotouh, Sawsan

2015-03-01

Several studies have pointed to the nicotinic acetylcholine receptor (nAChR) antagonists, such as mecamylamine (MEC), as a potential therapeutic target for the treatment of depression. The present study evaluated the behavioral and neurochemical effects of chronic administration of MEC (1, 2, and 4 mg/kg/day, intraperitoneally (i.p.)) in Wistar rats exposed to chronic restraint stress (CRS, 4 h × 6 W). MEC prevented CRS-induced depressive-like behavior via increasing sucrose preference, body weight, and forced swim test (FST) struggling and swimming while reducing immobility in FST and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity (adrenal gland weight and serum corticosterone). At the same time, MEC amended CRS-induced anxiety as indicated by decreasing central zone duration in open field test and increasing active interaction duration. Additionally, MEC modulated the prefrontal cortex (PFC) level of brain-derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), and norepinephrine (NE). In conclusion, the present data suggest that MEC possesses antidepressant and anxiolytic-like activities in rats exposed to CRS. These behavioral effects may be in part mediated by reducing HPA axis hyperactivity and increasing PFC level of BDNF and monoamines. Accordingly, these findings further support the hypothesis that nAChRs blockade might afford a novel promising strategy for pharmacotherapy of depression.

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

International Nuclear Information System (INIS)

Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

2012-01-01

Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

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Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

2014-01-01

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

Antidepressant-Like Effect of Lipid Extract of Channa striatus in Chronic Unpredictable Mild Stress Model of Depression in Rats

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Mohamed Saleem Abdul Shukkoor

2016-01-01

Full Text Available This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictable mild stress (CUMS model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus. The lipid extract of C. striatus (125, 250, and 500 mg/kg significantly (p<0.05 reversed all the above parameters in rats subjected to CUMS, thus exhibiting antidepressant-like effect. The mechanism was found to be mediated through decrease in plasma corticosterone, increase in serotonin levels in prefrontal cortex, increase in dopamine and noradrenaline levels in hippocampus and prefrontal cortex, increase in BDNF in hippocampus and prefrontal cortex, and decrease in IL-6 and NF-κB in prefrontal cortex.

Can prenatal low-dose irradiation affect behavior of adult rats?

International Nuclear Information System (INIS)

Smajda, B.; Tomasova, L.; Kokocova, N.

2011-01-01

The aim of our study was to determine whether exposure of very low dose gamma-rays during the critical phase of brain development affects some selected behavioral parameters in adult rats. Pregnant female Wistar rats were irradiated with 1 Gy gamma-rays from a cobalt source at 17 th day of pregnancy. The progeniture of irradiated as well as non-irradiated females have undergone behavioral tests at the age of 3 months. Irradiated animals exhibited lower locomotor and exploratory activity in the open field test. (authors)

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

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

2017-12-13

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

5-Aza-2'-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats.

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Xiaomeng Qiao

Full Text Available Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc, an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC. Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test. We found that 5-Aza-dc injection into the mPFC significantly decreased alcohol consumption and alcohol preference in alcohol-exposure rats, corresponding to the reduced blood alcohol levels. Although 5-Aza-dc potentiated the anxiety-like behavior of alcohol-exposure rats, it had no effect on the locomotor activity. Moreover, both of the mRNA and protein levels of DNA Methyltransferase 3A (DNMT3A and DNMT3B in the mPFC were upregulated after 35 days of alcohol exposure and this upregulation could be reversed by 5-Aza-dc treatment. Additionally, 5-Aza-dc reversed the alcohol-induced downregulation of neurotrophin-3 (Ntf3, correspondingly the expression of its receptor-TrkC was reduced. These findings identified a functional role of 5-Aza-dc in alcohol-related behavioral phenotypes and one of the potential target genes, Ntf3. We also provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcohol abuse.

Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats.

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Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta

2014-07-01

The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

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Del Arco, Alberto; Ronzoni, Giacomo; Mora, Francisco

2015-07-01

A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

Science.gov (United States)

van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

2015-07-08

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning.

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Sandrini, Marco; Manenti, Rosa; Brambilla, Michela; Cobelli, Chiara; Cohen, Leonardo G; Cotelli, Maria

2016-03-01

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Competition among oxidizable substrates in brains of young and adult rats. Dissociated cells.

OpenAIRE

Roeder, L M; Tildon, J T; Holman, D C

1984-01-01

The rates of conversion of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine into 14CO2 were measured in the presence and absence of alternative oxidizable substrates in intact dissociated cells from the brains of young and adult rats. When unlabelled glutamine was added to [6-14C]glucose or unlabelled glucose was added to [U-14C]glutamine, the rate of 14CO2 production was decreased in both young and adult rats. The rate of oxidation of 3-hydroxy[3-14C]b...

Contributions of the Hippocampus and Medial Prefrontal Cortex to Energy and Body Weight Regulation

Science.gov (United States)

Davidson, T. L.; Chan, Kinho; Jarrard, Leonard E.; Kanoski, Scott E.; Clegg, Deborah J.; Benoit, Stephen C.

2008-01-01

The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared to controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared to control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior. PMID:18831000

Repeated Blockade of NMDA Receptors during Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex

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Jitao eLi

2016-03-01

Full Text Available Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg, a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV-, calbindin (CB- and calretinin (CR-positive neurons in mPFC were analyzed at either 24 hours or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV+ and CB+ neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV+ and CB+ neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

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Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

2015-08-30

Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

International Nuclear Information System (INIS)

Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

1979-01-01

We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

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Nicole L Nichols

Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

International Nuclear Information System (INIS)

Castro, Beatriz; Sánchez, Pilar; Torres, Jesús M.; Ortega, Esperanza

2015-01-01

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

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Castro, Beatriz; Sánchez, Pilar [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada (Spain); Torres, Jesús M., E-mail: torrespi@ugr.es [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada (Spain); Institute of Neurosciences, Faculty of Medicine, University of Granada, Granada (Spain); Ortega, Esperanza, E-mail: esortega@ugr.es [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada (Spain); Institute of Neurosciences, Faculty of Medicine, University of Granada, Granada (Spain)

2015-10-15

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin

Influx mechanisms in the embryonic and adult rat choroid plexus

DEFF Research Database (Denmark)

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

2015-01-01

The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

Differential effects of magnetic field exposure from domestic power supply on loco motor and exploratory behavior of an adult rat

International Nuclear Information System (INIS)

Anandavadivel, A.; Caleo, M.

2011-01-01

In the present study, we have examined the low intense magnetic field exposed on adult rats to understand effect of several behavioral parameters. The rats are tested in the open field and spontaneous alternation task after either a single or chronic exposure to the magnetic field. We found that magnetic field exposure had no effect on locomotor behavior in the adult. However, the exploratory behavior of adult rats in the open field was significantly affected. Indeed, we found a consistent increase in behavior performance viz. exploration time and number of exploration events in rats exposed to magnetic field. Our results demonstrate behavioral changes after magnetic field exposure in adult subjects. This also suggests possible deleterious effects of magnetic field exposure in the brain. (author)

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

Science.gov (United States)

Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Measurement of the frontal and prefrontal lobe volumes in children with malnutrition by three dimensional magnetic resonance imaging scan].

Science.gov (United States)

Kanemura, Hideaki; Aihara, Masao; Nakazawa, Shinpei

2002-09-01

To evaluate the effects of malnutrition in early life on the growth of the frontal and prefrontal lobes, we quantitatively measured the volumes of the frontal and prefrontal lobes by three dimensional (3-D) MRI in three children (1 year 2 months to 2 years 5 months) with malnutrition. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. The data obtained were compared with those of 16 normal subjects (13 children aged 5 months to 14 years, and 3 adults aged 27 to 39 years). The volumes of the frontal and prefrontal lobes in the subjects were smaller compared with age matched controls. The results suggest that malnutrition in early life affects the growth of the frontal and prefrontal lobes.

Comparison of stress-induced changes in adults and pups: is aldosterone the main adrenocortical stress hormone during the perinatal period in rats?

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János Varga

Full Text Available Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR and mineralocorticoid receptors (MR and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2, an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

Science.gov (United States)

Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

2007-01-01

Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

Science.gov (United States)

Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

2017-01-01

DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

Science.gov (United States)

Mendoza, J; Sanio, C; Chaudhri, N

2015-02-01

The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted. Copyright © 2014 Elsevier Inc. All rights reserved.

The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats.

Science.gov (United States)

Dahlquist, G; Persson, B

1976-11-01

Cerebral blood flow (CBF) was measured by means of Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(1-methylpropyl)2-thiobarbituric acid. Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr. The mean CBF values of 0.48+/-0.04 and 0.62+/-0.07 ml/(g X min), +/- SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation. At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-beta-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-beta-hydroxybutyrate only in infant animals. In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA X min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA X min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

OpenAIRE

Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

1988-01-01

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

Science.gov (United States)

Thornton, S N; Padzys, G S; Trabalon, M

2014-05-01

The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult. Copyright © 2014 Elsevier Inc. All rights reserved.

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.

Science.gov (United States)

Zaidan, Hiba; Ramaswami, Gokul; Golumbic, Yaela N; Sher, Noa; Malik, Assaf; Barak, Michal; Galiani, Dalia; Dekel, Nava; Li, Jin B; Gaisler-Salomon, Inna

2018-01-08

Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels. In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes. Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.

Requiring collaboration: Hippocampal-prefrontal networks needed in spatial working memory and ageing. A multivariate analysis approach.

Science.gov (United States)

Zancada-Menendez, C; Alvarez-Suarez, P; Sampedro-Piquero, P; Cuesta, M; Begega, A

2017-04-01

Ageing is characterized by a decline in the processes of retention and storage of spatial information. We have examined the behavioural performance of adult rats (3months old) and aged rats (18months old) in a spatial complex task (delayed match to sample). The spatial task was performed in the Morris water maze and consisted of three sessions per day over a period of three consecutive days. Each session consisted of two trials (one sample and retention) and inter-session intervals of 5min. Behavioural results showed that the spatial task was difficult for middle aged group. This worse execution could be associated with impairments of processing speed and spatial information retention. We examined the changes in the neuronal metabolic activity of different brain regions through cytochrome C oxidase histochemistry. Then, we performed MANOVA and Discriminant Function Analyses to determine the functional profile of the brain networks that are involved in the spatial learning of the adult and middle-aged groups. This multivariate analysis showed two principal functional networks that necessarily participate in this spatial learning. The first network was composed of the supramammillary nucleus, medial mammillary nucleus, CA3, and CA1. The second one included the anterior cingulate, prelimbic, and infralimbic areas of the prefrontal cortex, dentate gyrus, and amygdala complex (basolateral l and central subregions). There was a reduction in the hippocampal-supramammilar network in both learning groups, whilst there was an overactivation in the executive network, especially in the aged group. This response could be due to a higher requirement of the executive control in a complex spatial memory task in older animals. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo and in vitro dermal penetration of 2,4,5,2',4', 5'-hexachlorobiphenyl in young and adult rats

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Shah, P.V.; Sumler, M.R.; Fisher, H.L.; Hall, L.L.

1989-01-01

Penetration of 2,4,5,2',4',5'-[ 14 C]hexachlorobiphenyl (HCB) through skin of young (33 days) and adult (82 days) female Fischer 344 rats was determined in vivo and by two in vitro methods. In vivo dermal penetration at 120 hr was 45% in young and 43% in adults. At 72 hr in vivo dermal penetration was 35% in young and 26% in adults compared to 1.5% for young and 1.0% for adult as measured with a continuous flow in vitro system and 2.9% for young and 1.9% for adults as measured with a static in vitro system. Most of the dermally absorbed HCB remained in the body as only 4.9 and 2.6% of that absorbed was excreted by young and adult rats, respectively, at the end of 120 hr. Significant differences in dermal penetration and kinetics of HCB between young and adult female rats were observed. The elimination of ECB-derived material was approximately six times higher in feces than in urine. A physiological pharmacokinetic model was fitted to the organ and tissue radioactivity distribution data. Parameters in the model determined from dermal dosing of female Fischer 344 rats were in reasonable agreement with those reported in the literature for adult male Sprague-Dawley rats (iv dose). The rate constant for dermal penetration was 0.83 x 10 -4 min -1 for adults and 0.96 x 10 -4 min -1 for young. The delay or lag time parameter for dermal penetration was 4.4 hr in adults and 1.1 hr in young

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

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Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

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Irmgard eAmrein

2014-05-01

Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

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Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

2014-01-01

African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

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T.C. Peixoto

2018-04-01

Full Text Available Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

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Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

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Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

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Anne Klomp

Full Text Available The antidepressant drug fluoxetine (Prozac has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b effects on tryptophan hydroxylase (TPH expression, a measure of serotonin synthesis; c whether treatment effects during adolescence differed from treatment at an adult age, and d whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+ cells and of the number of young migratory neurons (doublecortin+, revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Effect of modafinil on learning performance and neocortical long-term potentiation in rats.

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Burgos, Héctor; Castillo, Amparo; Flores, Osvaldo; Puentes, Gustavo; Morgan, Carlos; Gatica, Arnaldo; Cofré, Christian; Hernández, Alejandro; Laurido, Claudio; Constandil, Luis

2010-10-30

Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4×4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied. Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

Electrophysiological evidence during episodic prospection implicates medial prefrontal and bilateral middle temporal gyrus.

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Hsu, Chia-Fen; Sonuga-Barke, Edmund J S

2016-08-01

fMRI studies have implicated the medial prefrontal cortex and medial temporal lobe, components of the default mode network (DMN), in episodic prospection. This study compared quantitative EEG localized to these DMN regions during prospection and during resting and while waiting for rewards. EEG was recorded in twenty-two adults while they were asked to (i) envision future monetary episodes; (ii) wait for rewards and (iii) rest. Activation sources were localized to core DMN regions. EEG power and phase coherence were compared across conditions. Prospection, compared to resting and waiting, was associated with reduced power in the medial prefrontal gyrus and increased power in the bilateral medial temporal gyrus across frequency bands as well as greater phase synchrony between these regions in the delta band. The current quantitative EEG analysis confirms prior fMRI research suggesting that medial prefrontal and medial temporal gyrus interactions are central to the capacity for episodic prospection. Copyright © 2016 Elsevier B.V. All rights reserved.

Prefrontal cortex, caloric restriction and stress during aging: studies on dopamine and acetylcholine release, BDNF and working memory.

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Del Arco, Alberto; Segovia, Gregorio; de Blas, Marta; Garrido, Pedro; Acuña-Castroviejo, Dario; Pamplona, Reinald; Mora, Francisco

2011-01-01

This study was designed to investigate whether long-term caloric restriction during the life span of the rat changes the effects of an acute mild stress on the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and on working memory performance. Spontaneous motor activity was also monitored and levels of BDNF measured in the prefrontal cortex, amygdala and hippocampus. Male Wistar rats (3 months of age) were housed during 3, 12, 21 and 27 months (6, 15, 24 and 30 months of age at the end of housing) in caloric restriction (CR; 40% food intake restriction) or control conditions. After behavioural testing, animals were further subdivided into two other groups. In one of the groups BDNF protein levels were determined. In the other group rats were implanted with guide cannulas into the PFC to perform microdialysis experiments. In CR rats the release of dopamine produced by handling stress did not differ from the response found in control rats of 6, 15 and 24 months of age. The release of acetylcholine was not changed at the ages of 6 and 15 months but reduced at the age of 24 months. Stress did not change dopamine or acetylcholine release in CR and control rats of 30 months of age. BDNF levels were increased in the hippocampus and amygdala, but not in the PFC, of 6 and 15 months CR rats. Spontaneous motor activity was increased in all groups of CR rats. Age, however, decreased motor activity in CR and control rats. Both experimental groups showed similar working memory performance in a delayed alternation task in basal conditions and after a situation of acute stress. These results suggest that CR does not modify the function of the PFC in response to an acute stress nor the changes found as a result of the normal process of aging. Copyright © 2010 Elsevier B.V. All rights reserved.

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats.

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Conceição, C Q; Engi, S A; Cruz, F C; Planeta, C S

2017-11-17

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats

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Raffaella Crescenzo

2018-04-01

Full Text Available The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism. Therefore, the aim of this study was to compare the metabolic changes induced by the fructose-rich diet in rats of different age, i.e., young (30 days old and adult (90 days old rats. The fructose-rich diet increased whole body lipid content in adult, but not in young rats. The analysis of liver markers of inflammation suggests that different mechanisms depending on the age might be activated after the fructose-rich diet. In fact, a pro-inflammatory gene-expression analysis showed just a minor activation of macrophages in young rats compared to adult rats, while other markers of low-grade metabolic inflammation (TNF-alpha, myeloperoxidase, lipocalin, haptoglobin significantly increased. Inflammation was associated with oxidative damage to hepatic lipids in young and adult rats, while increased levels of hepatic nitrotyrosine and ceramides were detected only in young rats. Interestingly, fructose-induced hepatic insulin resistance was evident in young but not in adult rats, while whole body insulin sensitivity decreased both in fructose-fed young and adult rats. Taken together, the present data indicate that young rats do not increase their body lipids but are exposed to metabolic perturbations, such as hepatic insulin resistance and hepatic oxidative stress, in line with the finding that increased fructose intake may be an important predictor of metabolic risk in young people, independently of weight status. These results indicate the need of corrective

Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

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Peterson, Bethany L; Park, Thomas J; Larson, John

2012-01-11

Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Electrophysiological mapping of novel prefrontal - cerebellar pathways

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Thomas C Watson

2009-08-01

Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment.

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van Harmelen, Anne-Laura; van Tol, Marie-José; Dalgleish, Tim; van der Wee, Nic J A; Veltman, Dick J; Aleman, André; Spinhoven, Philip; Penninx, Brenda W J H; Elzinga, Bernet M

2014-12-01

Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional face processing. However, no study has yet investigated the functional neural correlates of neutral and emotional memory in adults reporting CEM. Using functional magnetic resonance imaging, we investigated CEM-related differential activations in mPFC during the encoding and recognition of positive, negative and neutral words. The sample (N = 194) consisted of patients with depression and/or anxiety disorders and healthy controls (HC) reporting CEM (n = 96) and patients and HC reporting no abuse (n = 98). We found a consistent pattern of mPFC hypoactivation during encoding and recognition of positive, negative and neutral words in individuals reporting CEM. These results were not explained by psychopathology or severity of depression or anxiety symptoms, or by gender, level of neuroticism, parental psychopathology, negative life events, antidepressant use or decreased mPFC volume in the CEM group. These findings indicate mPFC hypoactivity in individuals reporting CEM during emotional and neutral memory encoding and recognition. Our findings suggest that CEM may increase individuals' risk to the development of psychopathology on differential levels of processing in the brain; blunted mPFC activation during higher order processing and enhanced amygdala activation during automatic/lower order emotion processing. These findings are vital in understanding the long-term consequences of CEM. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

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Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

2014-06-01

Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

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Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

2016-02-01

Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

Oxytocin in the amygdala and not the prefrontal cortex enhances fear and impairs extinction in the juvenile rat.

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Kritman, Milly; Lahoud, Nisrine; Maroun, Mouna

2017-05-01

A growing body of evidence suggests that the hypothalamic neuropeptide oxytocin (OT), aside from its central role in the regulation of social behavior, reduces fear and anxiety. The functional and opposing interactions of the medial prefrontal cortex (mPFC) and the amygdala in regulation of fear provide a unique experimental setting to examine the effects of OT on fear and extinction. Recent evidence suggests that in the adult animal OT can play a dual role in the regulation of fear leading to contrasting effects on fear depending on the manipulated brain region and the time of manipulations. The OT system is one of the systems that undergoes major changes throughout development, however, its role in regulating fear in young animals has not been widely explored. We recently showed that the mechanisms of extinction, and specifically engagement of the mPFC in extinction, are not identical in adult and juvenile animals. Thus, the purpose of this study was to elucidate the effects of OT on fear and extinction in juvenile animals. To that end, we determine extinction, by measuring freezing at different time points, following microinjection of the OT agonist, TGOT, into the mPFC, the basolateral and the central nuclei of the amygdala (BLA and CeA, respectively). The results show that whereas TGOT microinjections into the IL-mPFC did not affect extinction, microinjections into the amygdala were mainly associated with enhanced fear and impaired extinction. These results further emphasize the differences between adult and juvenile brains. Copyright © 2017. Published by Elsevier Inc.

Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

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Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

2016-03-15

Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic desipramine treatment alters tyrosine hydroxylase but not norepinephrine transporter immunoreactivity in norepinephrine axons in the rat prefrontal cortex

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Erickson, Susan L.; Gandhi, Anjalika R.; Asafu-Adjei, Josephine K.; Sampson, Allan R.; Miner, LeeAnn; Blakely, Randy D.; Sesack, Susan R.

2011-01-01

Pharmacological blockade of norepinephrine (NE) reuptake is clinically effective in treating several mental disorders. Drugs that bind to the NE transporter (NET) alter both protein levels and activity of NET and also the catecholamine synthetic enzyme tyrosine hydroxylase (TH). We examined the rat prefrontal cortex (PFC) by electron microscopy to determine whether the density and subcellular distribution of immunolabeling for NET and colocalization of NET with TH within individual NE axons were altered by chronic treatment with the selective NE uptake inhibitor desipramine (DMI). Following DMI treatment (21 days, 15 mg/kg/day), NET-immunoreactive (-ir) axons were significantly less likely to colocalize TH. This finding is consistent with reports of reduced TH levels and activity in the locus coeruleus after chronic DMI and indicates a reduction of NE synthetic capacity in the PFC. Measures of NET expression and membrane localization, including the number of NET-ir profiles per tissue area sampled, the number of gold particles per NET-ir profile area, and the proportion of gold particles associated with the plasma membrane, were similar in DMI and vehicle treated rats. These findings were verified using two different antibodies directed against distinct epitopes of the NET protein. The results suggest that chronic DMI treatment does not reduce NET expression within individual NE axons in vivo or induce an overall translocation of NET protein away from the plasma membrane in the PFC as measured by ultrastructural immunogold labeling. Our findings encourage consideration of possible postranslational mechanisms for regulating NET activity in antidepressant-induced modulation of NE clearance. PMID:21208501

Reorganization of auditory map and pitch discrimination in adult rats chronically exposed to low-level ambient noise

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Weimin eZheng

2012-09-01

Full Text Available Behavioral adaption to a changing environment is critical for an animal’s survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment.

Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

International Nuclear Information System (INIS)

Krueger, Katharina; Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

2007-01-01

In this study, the effects of pentavalent dimethylarsinic acid ((CH 3 ) 2 AsO(OH); DMA V ) and trivalent dimethylarsinous acid ((CH 3 ) 2 As(OH); DMA III ) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 μmol/l. DMA V had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA III significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 μmol/l DMA III in adult and 10 μmol/l DMA III in young rats. Moreover, DMA III significantly affected the LTP-induction. Application of 10 μmol/l DMA III resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA III . In slices of young rats, the depressant effects of DMA III were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA V on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential

Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

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Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

2012-08-01

The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

The expression of NFATc1 in adult rat skeletal muscle fibres.

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Mutungi, Gabriel

2008-03-01

Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

Dobutamine stress echocardiography in healthy adult male rats

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Couet Jacques

2005-10-01

Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions.

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Seyed-Allaei, Shima; Avanaki, Zahra Nasiri; Bahrami, Bahador; Shallice, Tim

2017-07-01

An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35-39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

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Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Use of the light/dark test for anxiety in adult and adolescent male rats.

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Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

2013-11-01

The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence. Copyright © 2013 Elsevier B.V. All rights reserved.

Abstinence environment contributes to age differences in reinstatement of cocaine seeking between adolescent and adult male rats.

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Li, Chen; Frantz, Kyle J

2017-07-01

Extinction responding and cue-induced reinstatement of cocaine seeking after 60-days of forced abstinence are attenuated in male rats that self-administered cocaine during adolescence, compared with adults. Given that environmental enrichment during abstinence decreases reinstatement among adults, a possible explanation for attenuated reinstatement among adolescents is that standard pair-housing in prior studies creates a more stimulating environment for younger rats. Therefore, we tested whether standard pair-housing is necessary for the attenuated reinstatement among adolescents by determining whether an impoverished environment during abstinence would increase reinstatement among adolescents, up to adult levels. Conversely, we also tested whether environmental enrichment could further decrease reinstatement among adolescents, and whether we could replicate effects of environmental enrichment to decrease reinstatement among adults down to adolescent levels (positive controls). Adolescent and adult male Wistar rats self-administered cocaine intravenously for 12days (fixed ratio 1; 0.36mg/kg per infusion; 2h sessions). Rats were then moved into enriched (grouped, large cages, novel toys), standard (pair-housed, shoebox cages), or impoverished (isolated, hanging cages) housing conditions. After 60days, extinction and cue-induced reinstatement of cocaine seeking were tested, followed by drug-primed reinstatement (0, 5, 10mg/kg cocaine, i.p.). Consistent with previous results, extinction and cue-induced reinstatement were attenuated in adolescent-onset groups compared with adults; this age difference also extended to drug-primed reinstatement. In support of the present hypothesis, an impoverished environment during abstinence increased reinstatement among adolescents to levels that were not different from adult standard-housing levels. These data suggest that abstinence environment influences the enduring effects of cocaine among adolescents as well as adults

Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

International Nuclear Information System (INIS)

Krueger, Katharina; Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

2009-01-01

Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Muβhoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Muβhoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA V ) and monomethylarsonous acid (MMA III ) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA V had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA III strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 μmol/l (adult rats) and 25 μmol/l (young rats) and LTP amplitudes at concentrations of 25 μmol/l (adult rats) and 10 μmol/l (young rats), respectively. In contrast, application of 1 μmol/l MMA III led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Krueger, K., Gruner, J

HISTOLOGICAL STUDIES OF THE EFFECTS OF RED PEPPER ON THE STOMACH OF ADULT WISTAR RATS

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Josiah O. Adjene

2007-01-01

Full Text Available Histological effects of red pepper commonly used as spice in food on the stomach of adult wistar rats were carefully investigated. The rats of both sexes (n=24, average weight of 200g were randomly assigned into two treatments (n=16 and control (n=6 groups. The rats in the treatments groups received 1g and 2g of red pepper thoroughly mixed with 20g of their feeds for 7 and 14 days, while the control rats received equal amounts of feeds without the red pepper added. The rats were fed with grower's mash purchased from Edo feeds and flour mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day eight and fifteen of the experiment respectively.The stomach was carefully dissected out and quickly fixed in 10% formol saline for routine histological procedure after H & E method.The histological findings after H&E methods indicated that the treated sections of the stomach showed some level of cellular hypertrophy, congestion of blood vessels degenerative changes disruption and distortion of the cytoarchitecture of the stomach.These findings indicate that red pepper may have some deleterious effects on the microanatomy of the stomach of adult wistar rat at higher doses. It is recommended that further studies aimed at corroborating these findings be carried out.

Histological evaluation of the prefrontal cortex of infantile Wistar rats ...

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Primiparous Wistar rats were mated, and pregnancy was confirmed. A daily dose of 0.03 mg/kg of nicotine was administered intra-peritoneally to each treated rat for five consecutive days during their first two weeks of gestation. The rate of development and maturation of brain cells was reduced, as well as a reduction in the ...

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

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C.Q. Conceição

2017-11-01

Full Text Available The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days. After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Less effort, better results: how does music act on prefrontal cortex in older adults during verbal encoding? An fNIRS study.

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Laura eFerreri

2014-05-01

Full Text Available Several neuroimaging studies of cognitive ageing revealed deficits in episodic memory abilities as a result of prefrontal cortex (PFC limitations. Improving episodic memory performance despite PFC deficits is thus a critical issue in ageing research. Listening to music stimulates cognitive performance in several non-purely musical activities (e.g. language and memory. Thus, music could represent a rich and helpful source during verbal encoding and therefore help subsequent retrieval. Furthermore, such benefit could be reflected in less demand of PFC, which is known to be crucial for encoding processes. This study aimed to investigate whether music may improve episodic memory in older adults while decreasing the PFC activity.Sixteen healthy older adults (µ=64.5y encoded lists of words presented with or without a musical background while their dorsolateral PFC (DLPFC activity was monitored using a 8-channel continuous-wave near-infrared spectroscopy (NIRS system (Oxymon Mk III, Artinis, The Netherlands. Behavioral results indicated a better source memory performance for words encoded with music compared to words encoded with silence (p

Maternal Separation during Breastfeeding Induces Gender-Dependent Changes in Anxiety and the GABA-A Receptor Alpha-Subunit in Adult Wistar Rats.

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Diego Armando León Rodríguez

Full Text Available Different models of rodent maternal separation (MS have been used to investigate long-term neurobiological and behavioral changes, associated with early stress. However, few studies have involved the analysis of sex-related differences in central anxiety modulation. This study investigated whether MS during breastfeeding affected adult males and females in terms of anxiety and brain GABA-A receptor-alpha-subunit immunoreactivity. The brain areas analyzed were the amygdale (AM, hippocampus (HP, medial prefrontal cortex (mPFC, medial preoptic area (POA and paraventricular nucleus (PVN. Rats were housed under a reversed light/dark cycle (lights off at 7∶00 h with access to water and food ad libitum. Animals underwent MS twice daily during the dark cycle from postnatal day 1 to postnatal day 21. Behavior was tested when rats were 65-70 days old using the elevated plus maze and after brains were treated for immunohistochemistry. We found that separated females spent more time in the open arms and showed more head dipping behavior compared with controls. The separated males spent more time in the center of the maze and engaged in more stretching behavior than the controls. Immunohistochemistry showed that separated females had less immunostained cells in the HP, mPFC, PVN and POA, while separated males had fewer immunolabeled cells in the PFC, PVN and AM. These results could indicate that MS has gender-specific effects on anxiety behaviors and that these effects are likely related to developmental alterations involving GABA-A neurotransmission.

Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats.

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Bisby, Madelyne A; Baker, Kathryn D; Richardson, Rick

2018-04-01

NMDA receptors (NMDARs) are considered critical for the consolidation of extinction but recent work challenges this assumption. Namely, NMDARs are not required for extinction retention in infant rats as well as when extinction training occurs for a second time (i.e., reextinction) in adult rats. In this study, a possible third instance of NMDAR-independent extinction was tested. Although adolescents typically exhibit impaired extinction retention, rats that are conditioned as juveniles and then given extinction training as adolescents (JuvCond-AdolesExt) have good extinction retention. Unexpectedly, this good extinction retention is not associated with an up-regulation of a synaptic plasticity marker in the medial prefrontal cortex, a region implicated in extinction consolidation. In the current study, rats received either the noncompetitive NMDAR antagonist MK801 (0.1 mg/kg, s.c.) or saline before extinction training. In several experiments, rats conditioned and extinguished as juveniles, adolescents, or adults exhibited impaired extinction retention after MK801 compared to saline, but this effect was not observed in JuvCond-AdolesExt rats. Further experiments ruled out several alternative explanations for why NMDAR antagonism did not affect extinction retention in adolescents extinguishing fear learned as a juvenile. These results illustrate yet another circumstance in which NMDARs are not required for successful extinction retention and highlight the complexity of fear inhibition across development. © 2018 Bisby et al.; Published by Cold Spring Harbor Laboratory Press.

Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats.

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Ying Fan

Full Text Available Bisphenol A (BPA, an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0 received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1. The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

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Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

Effects of amphetamine administration on neurogenesis in adult rats

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Tomasz Stępień

2017-12-01

Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

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Sonali Ghosh

2017-05-01

Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation

OpenAIRE

Chaloner, A.; Rao, A.; Al-Chaer, E.D.; Meerveld, B. Greenwood-Van

2009-01-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liqui...

Differential effects of controllable stress exposure on subsequent extinction learning in adult rats

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Osnat eHadad-Ophir

2016-01-01

Full Text Available Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC, followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC, as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL, but not prelimbic (PL cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

Prefrontal cortical GABA modulation of spatial reference and working memory.

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Auger, Meagan L; Floresco, Stan B

2014-10-31

Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1-2 min intervals). Infusions of the GABAA receptor antagonist bicuculline (12.5-50 ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder. © The Author 2014. Published by Oxford University Press on behalf of CINP.

Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

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Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

2015-09-01

The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

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)

Effects of interaction of an early experience of reward through maternal contact or its denial with social stress during adolescence on the serotonergic system and the stress responsiveness of adult female rats.

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Raftogianni, A; Diamantopoulou, A; Alikaridis, F; Stamatakis, A; Stylianopoulou, F

2012-05-03

Experiences during critical periods, such as the neonatal and adolescence, play a critical role in determining adult stress-coping behavior. Based on the aforementioned we developed an experimental protocol, which included a neonatal experience and a social stress during adolescence. The serotonergic system is known as an important modulator of coping ability and, in general, emotional balance in both normal and pathological states, such as depression and anxiety, for which females are more vulnerable. Thus in the present work we used female rats and determined 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and 5-hydroxytryptamine receptor type 1A (5-HT(1A)) receptor levels in the prefrontal cortex (PFC) and the amygdala (AMY). During postnatal days 10-13 (PND 10-13) rat pups were exposed to a T-maze, one arm of which lead to the mother. One group of animals was allowed contact with the mother (rewarded-receiving expected reward (RER)), whereas the other was denied the expected reward (DER). High performance liquid chromatography (HPLC) analysis revealed that in both the PFC and in AMY, adult RER animals had higher basal 5-HT levels. Furthermore, in the AMY of this group of animals, higher levels of 5-HT(1A) receptors were detected by Western blot analysis. In adulthood rats were exposed to the Forced Swimming Test/Stress (FST/S). RER animals not exposed to the adolescent stress exhibited longer immobility time during both the first and second day of FST. Corticosterone levels following the FST fell faster in the DER animals. Adolescent stress affected the responses to the adult FSS only in the DER animals, which had decreased 5-HT in the AMY and increased immobility time on both days of the FST, compared with the DER, not stressed in adolescence. The phenotype of the DER animals is in line with the "match-mismatch" hypothesis, which states that if two events during critical periods of life "match" in being mildly stressful, their interaction can be adaptive. Copyright

The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

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Claudia G. Liberini

2016-10-01

Full Text Available Objective: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods: To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg, amylin plus the amylin receptor antagonist AC187 (500 μg/kg or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU technique. Results: Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats. Keywords: Amylin, Adult neurogenesis, Area postrema, BrdU, Circumventricular organs

Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

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Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake.

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Perry, Jennifer L; Anderson, Marissa M; Nelson, Sarah E; Carroll, Marilyn E

2007-05-16

Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats selectively bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consisted of two 6-h sessions. In the first 6 h, rats were given non-contingent cocaine infusions at random intervals 10 times per hour, and during the second 6-h session, rats were allowed to self-administer cocaine under a fixed ratio 1 (FR 1) lever-response contingency. Acquisition was defined as a total of at least 250 infusions over 5 consecutive days, and rats were given 30 days to meet the acquisition criterion. Subsequently, saccharin phenotype scores were determined by comparing 24-h saccharin and water consumption in two-bottle tests to verify HiS/LoS status. Adolescent LoS rats had a faster rate of acquisition of cocaine self-administration than adult LoS rats; however, adolescent and adult HiS rats acquired at the same rate. Both HiS and LoS adolescents had significantly higher saccharin phenotype scores than HiS and LoS adults, respectively. Additionally, saccharin score was negatively correlated with the number of days to meet the acquisition criterion for cocaine self-administration, but this was mostly accounted for by the HiS adolescents. These results suggest that during adolescence, compared with adulthood, rats have both an increased avidity for sweets and vulnerability to initiate drug abuse.

Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

DEFF Research Database (Denmark)

Bortz, D M; Mikkelsen, J D; Bruno, J P

2013-01-01

The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels...

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

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Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2016-02-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

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Boyd R Rorabaugh

Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

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Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

2017-01-01

Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.

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Schramm-Sapyta, Nicole L; DiFeliceantonio, Alexandra G; Foscue, Ethan; Glowacz, Susan; Haseeb, Naadeyah; Wang, Nancy; Zhou, Cathy; Kuhn, Cynthia M

2010-12-01

Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol. Copyright © 2010 by the Research Society on Alcoholism.

Negative Effect of Zinc on Testes, Testosterone and Gonadotrophins Levels in Adult Male Wistar Rats

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D. Sohrabi

2008-10-01

Full Text Available Background and ObjectivesThe toxic effects of zinc leading to sebaceous gland closure, skin eczema and blister have been previously demonstrated in other studies. The aim of this study is to determine the chronic effects of zinc chloride (ZnCl2 on testicular tissues, testosterone and gonadotrophins in adult male Wistar rats.Methods Twenty four Adult male Wistar rats were divided in to two groups of study and control with each group consisting of 12 rats. Study group rats received 10 mg/kg interaperitoneal Zinc chloride in normal saline (N.S every other day for 30 days. Control group rats received N.S during this time. Blood sample for hormonal evaluation were collected from hearts of these rats. The rats were destroyed and their testes were removed and fixed in a 10% formaldehyde and glutaraldehyde solution.ResultsThe results of this study showed a significant decrease in the level of LH and testosterone hormone among the rats in the study group compared to the control group with p< 0.001 and p< 0.01 respectively. Study of fine structure of testicular cells and tissues in the study group rats revealed swelling of mitochondria, increase in smooth endoplasmic reticulum vacuolization and lysosomic granules (Autophagic vacuoles in cytosol of their germinal cells.ConclusionBased on the results of this study consumption of large amount of compounds which contain zinc should be controlled and limited among men. There is a need for further studies to evaluate and determine the reversibility of most hormonal and physiological changes due to usage of zinc containing compounds.Keywords: Zinc Chloride; Testis; Testosterone; Gonadotrophins

Dorsolateral Prefrontal Contributions to Human Intelligence

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Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

2012-01-01

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control functions for human intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key competencies of general intelligence and executive function remains to be well established. Here we studied human brain lesion patients with dlPFC lesions to investigate whether this region is computationally necessary for performance on neuropsychological tests of general intelligence and executive function, administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions (n = 19), non-dlPFC lesions (n = 152), and no brain lesions (n = 55). The key results indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dlPFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. The observed findings support a central role for the dlPFC in general intelligence and make specific recommendations for the interpretation and application of the WAIS and D-KEFS to the study of high-level cognition in health and disease. PMID:22634247

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available   Abstract  Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex.

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Bassareo, Valentina; De Luca, Maria Antonietta; Di Chiara, Gaetano

2007-04-01

Conditioned stimuli (CSs) by pavlovian association with reinforcing drugs (US) are thought to play an important role in the acquisition, maintenance and relapse of drug dependence. The aim of this study was to investigate by microdialysis the impact of pavlovian drug CSs on behaviour and on basal and drug-stimulated dopamine (DA) in three terminal DA areas: nucleus accumbens shell, core and prefrontal cortex (PFCX). Conditioned rats were trained once a day for 3 days by presentation of Fonzies filled box (FFB, CS) for 10 min followed by administration of morphine (1 mg/kg), nicotine (0.4 mg/kg) or saline, respectively. Pseudo-conditioned rats were presented with the FFB 10 h after drug or saline administration. Rats were implanted with microdialysis probes in the shell, core and PFCX. The effect of stimuli conditioned with morphine and nicotine on DA and on DA response to drugs was studied. Drug CSs elicited incentive reactions and released DA in the shell and PFCX but not in the core. Pre-exposure to morphine CS potentiated DA release to morphine challenge in the shell but not in the core and PFCX. This effect was related to the challenge dose of morphine and was stimulus-specific since a food CS did not potentiate the shell DA response to morphine. Pre-exposure to nicotine CS potentiated DA release in the shell and PFCX. The results show that drug CSs stimulate DA release in the shell and medial PFCX and specifically potentiate the primary stimulant drug effects on DA transmission.

Effects of physical exercise on object recognition memory in adult rats of postnatal isoflurane exposures

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Xiao-yan FANG

2017-08-01

Full Text Available Objective To investigate effects of physical exercise (PE on object recognition memory in adult rats of postnatal isoflurane (Iso exposures. Methods One hundred and ten postnatal 7-day SD rats (P7 were randomly divided into four groups: normal control group (Naive, Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks, Iso group (three times of 2-hour Iso exposure in P7, P9, and P11, and Iso+PE group (received PE in P21 after postnatal Iso exposures. In P67, behavioral testing was conducted including open field and object recognition task (ORT, recording the time (Discrimination Ratios, DR that rats spent on exploring each object, evaluating effects of PE on object recognition memory. Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05. Compared with Naive, there was no group difference in DR (P>0.05 for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034. Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group: P67, P=0.050, P=0.017; P95, P=0.037, P=0.019; in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036, but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004. Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group: P=0.022, P=0.011; but in P95, the DR of non- Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE: P=0.008, P=0.017. Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

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Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

2015-01-01

Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

MS-377, a novel selective sigma(1) receptor ligand, reverses phencyclidine-induced release of dopamine and serotonin in rat brain.

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Takahashi, S; Horikomi, K; Kato, T

2001-09-21

A novel selective sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), inhibits phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced behaviors in animal models. In this study, we measured extracellular dopamine and serotonin levels in the rat brain after treatment with MS-377 alone, using in vivo microdialysis. We also examined the effects of MS-377 on extracellular dopamine and serotonin levels in the rat medial prefrontal cortex after treatment with PCP. MS-377 itself had no significant effects on dopamine release in the striatum (10 mg/kg, p.o.) nor on dopamine or serotonin release in the medial prefrontal cortex (1 and 10 mg/kg, p.o.). PCP (3 mg/kg, i.p.) markedly increased dopamine and serotonin release in the medial prefrontal cortex. MS-377 (1 mg/kg, p.o.), when administered 60 min prior to PCP, significantly attenuated this effect of PCP. These results suggest that the inhibitory effects of MS-377 on PCP-induced behaviors are partly mediated by inhibition of the increase in dopamine and serotonin release in the rat medial prefrontal cortex caused by PCP.

The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

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Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

2014-09-01

Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

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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.

Switch-task performance in rats is disturbed by 12 h of sleep deprivation but not by 12 h of sleep fragmentation.

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Leenaars, Cathalijn H C; Joosten, Ruud N J M A; Zwart, Allard; Sandberg, Hans; Ruimschotel, Emma; Hanegraaf, Maaike A J; Dematteis, Maurice; Feenstra, Matthijs G P; van Someren, Eus J W

2012-02-01

Task-switching is an executive function involving the prefrontal cortex. Switching temporarily attenuates the speed and/or accuracy of performance, phenomena referred to as switch costs. In accordance with the idea that prefrontal function is particularly sensitive to sleep loss, switch-costs increase during prolonged waking in humans. It has been difficult to investigate the underlying neurobiological mechanisms because of the lack of a suitable animal model. Here, we introduce the first switch-task for rats and report the effects of sleep deprivation and inactivation of the medial prefrontal cortex. Rats were trained to repeatedly switch between 2 stimulus-response associations, indicated by the presentation of a visual or an auditory stimulus. These stimulus-response associations were offered in blocks, and performance was compared for the first and fifth trials of each block. Performance was tested after exposure to 12 h of total sleep deprivation, sleep fragmentation, and their respective movement control conditions. Finally, it was tested after pharmacological inactivation of the medial prefrontal cortex. Controlled laboratory settings. 15 male Wistar rats. Both accuracy and latency showed switch-costs at baseline. Twelve hours of total sleep deprivation, but not sleep fragmentation, impaired accuracy selectively on the switch-trials. Inactivation of the medial prefrontal cortex by local neuronal inactivation resulted in an overall decrease in accuracy. We developed and validated a switch-task that is sensitive to sleep deprivation. This introduces the possibility for in-depth investigations on the neurobiological mechanisms underlying executive impairments after sleep disturbance in a rat model.

Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

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Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

2013-12-01

The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (Pmedulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH. © 2013.

Electroacupuncture Ameliorates Cognitive Deficit and Improves Hippocampal Synaptic Plasticity in Adult Rat with Neonatal Maternal Separation

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Lili Guo

2018-01-01

Full Text Available Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS. Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA group, and MS with Sham-EA treatment (MS + Sham-EA group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20 and Yintang (GV 29 during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity.

Reduced dorsolateral prefrontal cortical hemodynamic response in adult obsessive-compulsive disorder as measured by near-infrared spectroscopy during the verbal fluency task

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Hirosawa R

2013-07-01

Full Text Available Rikuei Hirosawa,1 Jin Narumoto,1 Yuki Sakai,1 Seiji Nishida,2 Takuya Ishida,1 Takashi Nakamae,1 Yuichi Takei,3 Kenji Fukui1 1Department of Psychiatry, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, 2Maizuru Medical Center, Kyoto, 3Department of Psychiatry and Neuroscience, Gunma University Graduate School of Medicine, Gunma, Japan Background: Near-infrared spectroscopy has helped our understanding of the neurobiological mechanisms of psychiatric disorders and has advantages including noninvasiveness, lower cost, and ease of use compared with other imaging techniques, like functional magnetic resonance imaging. The verbal fluency task is the most common and well established task used to assess cognitive activation during near-infrared spectroscopy. Recent functional neuroimaging studies have shown that the orbitofrontal cortex and other brain regions, including the dorsolateral prefrontal cortex, may play important roles in the pathophysiology of obsessive-compulsive disorder (OCD. This study aimed to evaluate hemodynamic responses in the dorsolateral prefrontal cortex in patients with OCD using near-infrared spectroscopy during the verbal fluency task and to compare these with dorsolateral prefrontal cortex responses in healthy controls. Methods: Twenty patients with OCD and 20 controls matched for age, gender, handedness, and estimated intelligence quotient participated in this study. The verbal fluency task was used to elicit near-infrared spectroscopic activation and consisted of a 30-second pre-task, followed by three repetitions of a 20-second verbal fluency task (total 60 seconds, followed by a 70-second post-task period. The near-infrared spectroscopy experiment was conducted on the same day as surveys of obsessive-compulsive symptoms, depression, and anxiety. Z-scores for changes in the concentration of oxygenated hemoglobin were compared between the OCD patients and controls in 14 channels set over the

A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

OpenAIRE

Ghanbari, H A; McCarl, R L

1980-01-01

A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

Negative Effect of Zinc on Testes, Testosterone and Gonadotrophins Levels in Adult Male Wistar Rats

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D Sohrabi

2012-05-01

Full Text Available

Background and Objectives

The toxic effects of zinc leading to sebaceous gland closure, skin eczema and blister have been previously demonstrated in other studies. The aim of this study is to determine the chronic effects of zinc chloride (ZnCl₂   on testicular tissues, testosterone and gonadotrophins in adult male Wistar rats.

Methods

Twenty four Adult male Wistar rats were divided in to two groups of study and control with each group consisting of 12 rats. Study group rats received 10 mg/kg interaperitoneal Zinc chloride in normal saline (N.S every other day for 30 days. Control group rats received N.S during this time. Blood sample for hormonal evaluation were collected from hearts of these rats. The rats were destroyed and their testes were removed and fixed in a 10% formaldehyde and glutaraldehyde solution.

Results

The results of this study showed a significant decrease in the level of LH and testosterone hormone among the rats in the study group compared to the control group with p< 0.001  and

p< 0.01 respectively. Study of fine structure of testicular cells and tissues in the study group rats  revealed swelling of mitochondria, increase in smooth endoplasmic reticulum vacuolization and lysosomic granules (Autophagic vacuoles in cytosol of their germinal cells.

Conclusion

Based on the results of this study consumption of large amount of compounds which contain zinc should be controlled and limited among men. There is a need for further studies to evaluate and determine the reversibility of most hormonal and physiological changes due to usage of zinc containing compounds.

Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia.

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Zoladz, Phillip R; Park, Collin R; Halonen, Joshua D; Salim, Samina; Alzoubi, Karem H; Srivareerat, Marisa; Fleshner, Monika; Alkadhi, Karim A; Diamond, David M

2012-03-01

We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing. Copyright © 2011 Wiley Periodicals, Inc.

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

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Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

2007-09-15

Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

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Schorn, Julia M.; Moyer, Eric L.; Lowe, Moniece M.; Morgan, Jonathan; Tulbert, Christina D.; Olson, John; Olson, John; Horita, David A.; Kleven, Gale A.

2017-01-01

As human habitation and eventual colonization of space becomes an inevitable reality, there is a necessity to understand how organisms develop over the life span in the space environment. Microgravity, altered CO2, radiation and psychological stress are some of the key factors that could affect mammalian reproduction and development in space, however there is a paucity of information on this topic. Here we combine early (neonatal) in vivo spectroscopic imaging with an adult emotionality assay following a common obstetric complication (prenatal asphyxia) likely to occur during gestation in space. The neural metabolome is sensitive to alteration by degenerative changes and developmental disorders, thus we hypothesized that that early neonatal neurometabolite profiles can predict adult response to novelty. Late gestation fetal rats were exposed to moderate asphyxia by occluding the blood supply feeding one of the rats pair uterine horns for 15min. Blood supply to the opposite horn was not occluded (within-litter cesarean control). Further comparisons were made with vaginal (natural) birth controls. In one-week old neonates, we measured neurometabolites in three brain areas (i.e., striatum, prefrontal cortex, and hippocampus). Adult perinatally-asphyxiated offspring exhibited greater anxiety-like behavioral phenotypes (as measured the composite neurobehavioral assay involving open field activity, responses to novel object, quantification of fecal droppings, and resident-intruder tests of social behavior). Further, early neurometabolite profiles predicted adult responses. Non-invasive MRS screening of mammalian offspring is likely to advance ground-based space analogue studies informing mammalian reproduction in space, and achieving high-priority.

Inactivation of the Medial-Prefrontal Cortex Impairs Interval Timing Precision, but Not Timing Accuracy or Scalar Timing in a Peak-Interval Procedure in Rats

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Catalin V. Buhusi

2018-06-01

Full Text Available Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a peak-interval (PI procedure. Reversible mPFC inactivation using GABA agonist muscimol resulted in decreased timing precision, with no effect on timing accuracy and scalar timing. These results are partly at odds with studies suggesting that ramping prefrontal activity is crucial to timing but closely match simulations with the Striatal Beat Frequency (SBF model proposing that timing is coded by the coincidental activation of striatal neurons by cortical inputs. Computer simulations indicate that in SBF, gradual inactivation of cortical inputs results in a gradual decrease in timing precision with preservation of timing accuracy and scalar timing. Further studies are needed to differentiate between timing models based on coincidence detection and timing models based on ramping mPFC activity, and clarify whether mPFC is specifically involved in timing, or more generally involved in attention, working memory, or response selection/inhibition.

MRI volumetry of prefrontal cortex

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Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

1995-05-01

Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

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Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

2015-01-01

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

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Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

2016-10-25

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex

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Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

2016-01-01

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life. PMID:27791080

Effect of dietary iron loading on recognition memory in growing rats.

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Murui Han

Full Text Available While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored. To characterize the role of dietary iron loading in memory function in the young, weanling rats were fed iron-loading diet (10,000 mg iron/kg diet or iron-adequate control diet (50 mg/kg for one month, during which a battery of behavioral tests were conducted. Iron-loaded rats displayed elevated non-heme iron levels in serum and liver, indicating a condition of systemic iron overload. In the brain, non-heme iron was elevated in the prefrontal cortex of iron-loaded rats compared with controls, whereas there was no difference in iron content in other brain regions between the two diet groups. While iron loading did not alter motor coordination or anxiety-like behavior, iron-loaded rats exhibited a better recognition memory, as represented by an increased novel object recognition index (22% increase from the reference value than control rats (12% increase; P=0.047. Western blot analysis showed an up-regulation of dopamine receptor 1 in the prefrontal cortex from iron-loaded rats (142% increase; P=0.002. Furthermore, levels of glutamate receptors (both NMDA and AMPA and nicotinic acetylcholine receptor (nAChR were significantly elevated in the prefrontal cortex of iron-loaded rats (62% increase in NR1; 70% increase in Glu1A; 115% increase in nAChR. Dietary iron loading also increased the expression of NMDA receptors and nAChR in the hippocampus. These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance. Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the

Eating high fat chow decreases dopamine clearance in adolescent and adult male rats but selectively enhances the locomotor stimulating effects of cocaine in adolescents.

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Baladi, Michelle G; Horton, Rebecca E; Owens, William A; Daws, Lynette C; France, Charles P

2015-03-24

Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats. Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow). Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow. These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Working Memory in the Prefrontal Cortex

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Funahashi, Shintaro

2017-01-01

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified. PMID:28448453

Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances ΔFosB expression in adult rats.

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Perondi, María Cecilia; Gutiérrez, María Cecilia; Valdomero, Analía; Cuadra, Gabriel Ricardo

2017-08-30

Previous studies have indicated that neural changes induced by early nutritional insult cause an altered response to pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal protein malnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed to morphine. Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day for three days with increasing doses of morphine or with saline. After 3days, the incentive motivational effects of cocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals, dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg, while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore, when animals of both groups were pre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine was elicited only in D-rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same experimental conditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecular substrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessed in different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens, amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivation facilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with an upregulation of ΔFosB in brain areas related to the reward circuitry. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

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Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

2017-02-01

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

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Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

2017-01-06

In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

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A.O. Eweka.

2008-01-01

Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

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J.O. Adjene

2010-01-01

Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

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Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

2017-01-01

After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

Prefrontal-Amygdala Connectivity and State Anxiety during Fear Extinction Recall in Adolescents

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Despina E. Ganella

2017-12-01

Full Text Available While deficits in fear extinction recall have been suggested to underlie vulnerability to anxiety disorders in adolescents, the neurobiology of these deficits remain underexplored. Here we investigate the functional connectivity (FC of the ventromedial prefrontal cortex (vmPFC and dorsolateral PFC (dlPFC underlying extinction recall in healthy adolescents, and assess associations between FC and state/trait anxiety. Adolescents (17 and adults (14, for comparison completed a fear-learning paradigm involving extinction and extinction recall during a functional magnetic resonance imaging session, in which skin conductance response (SCR was recorded. Psychophysiological interaction analyses revealed that during extinction recall there was significant negative connectivity between the vmPFC and amygdala in adults, but not adolescents. vmPFC-amygdala connectivity was positively correlated with SCR. Adolescents showed significant negative FC between the dlPFC and the left and right hippocampus, and the amygdala, which was positively correlated with state anxiety. Recall was also associated with negative connectivity between the dlPFC and thalamus, posterior cingulate cortex, fusiform gyrus, and pallidum in adolescents. These results demonstrate that fear extinction recall in healthy adolescents is associated with FC between prefrontal and limbic brain regions, and suggest that alterations in connectivity may be associated with vulnerability to anxiety in adolescence.

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

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Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

Structural and functional alterations in the prefrontal cortex after post-weaning social isolation: relationship with species-typical and deviant aggression.

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Biro, Laszlo; Toth, Mate; Sipos, Eszter; Bruzsik, Biborka; Tulogdi, Aron; Bendahan, Samuel; Sandi, Carmen; Haller, Jozsef

2017-05-01

Although the inhibitory control of aggression by the prefrontal cortex (PFC) is the cornerstone of current theories of aggression control, a number of human and laboratory studies showed that the execution of aggression increases PFC activity; moreover, enhanced activation was observed in aggression-related psychopathologies and laboratory models of abnormal aggression. Here, we investigated these apparently contradictory findings in the post-weaning social isolation paradigm (PWSI), an established laboratory model of abnormal aggression. When studied in the resident-intruder test as adults, rats submitted to PWSI showed increased attack counts, increased share of bites directed towards vulnerable body parts of opponents (head, throat, and belly) and reduced social signaling of attacks. These deviations from species-typical behavioral characteristics were associated with a specific reduction in the thickness of the right medial PFC (mPFC), a bilateral decrease in dendritic and glial density, and reduced vascularization on the right-hand side of the mPFC. Thus, the early stressor interfered with mPFC development. Despite these structural deficits, aggressive encounters enhanced the activation of the mPFC in PWSI rats as compared to controls. A voxel-like functional analysis revealed that overactivation was restricted to a circumscribed sub-region, which contributed to the activation of hypothalamic centers involved in the initiation of biting attacks as shown by structural equation modeling. These findings demonstrate that structural alterations and functional hyperactivity can coexist in the mPFC of rats exposed to early stressors, and suggest that the role of the mPFC in aggression control is more complex than suggested by the inhibitory control theory.

Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

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Maggio, Nicola; Segal, Menahem

2011-04-15

The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cognitive impact of social stress and coping strategy throughout development.

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Snyder, Kevin P; Barry, Mark; Valentino, Rita J

2015-01-01

Stress experience during adolescence has been linked to the development of psychiatric disorders in adulthood, many of which are associated with impairments in prefrontal cortex function. The current study was designed to determine the immediate and enduring effects of repeated social stress on a prefrontal cortex-dependent cognitive task. Early adolescent (P28), mid-adolescent (P42), and adult (P70) rats were exposed to resident-intruder stress for 5 days and tested in an operant strategy-shifting task (OSST) during the following week or several weeks later during adulthood. Engagement of prefrontal cortical neurons during the task was assessed by expression of the immediate early gene, c-fos. Social stress during adolescence had no immediate effects on task performance, but impaired strategy-shifting in adulthood, whereas social stress that occurred during adulthood had no effect. The cognitive impairment produced by adolescent social stress was most pronounced in rats with a passive coping strategy. Notably, strategy-shifting performance was positively correlated with medial prefrontal cortical c-fos in adulthood but not in adolescence, suggesting that the task engages different brain regions in adolescents compared to adults. Adolescent social stress produces a protracted impairment in prefrontal cortex-mediated cognition that is related to coping strategy. This impairment may be selectively expressed in adulthood because prefrontal cortical activity is integral to task performance at this age but not during adolescence.

Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

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Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

2013-01-01

The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats

NARCIS (Netherlands)

van Bennekum, A. M.; Wong Yen Kong, L. R.; Gijbels, M. J.; Tielen, F. J.; Roholl, P. J.; Brouwer, A.; Hendriks, H. F.

1991-01-01

The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in

A combined phytohemagglutinin and a-ketoglutarate pharmacology study of gut morphology and growth in older adult rats

DEFF Research Database (Denmark)

Filip, R.; Harrison, Adrian Paul; Pierzynowski, S.G.

2008-01-01

This study has evaluated the effect of phytohaemagglutinin (PHA) in combination with alpha-ketoglutaric acid (AKG), on GI-tract morphology and N balance in adult rats. Rats, aged approx. 15 months, were assigned to one of four experimental groups, (1) Control group, (2) AKG group, (3) AKG+PHA 100...

The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

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Willcocks, Andrea L; McNally, Gavan P

2013-01-01

The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

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Dacić Sanja

2008-01-01

Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

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Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

2015-01-01

The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress...

Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

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Moisala, M; Salmela, V; Hietajärvi, L; Salo, E; Carlson, S; Salonen, O; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

2016-07-01

The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings. Copyright © 2016 Elsevier Inc. All rights reserved.

The behavioral and molecular evaluation of effects of social instability stress as a model of stress-related disorders in adult female rats.

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Nowacka-Chmielewska, Marta Maria; Kasprowska-Liśkiewicz, Daniela; Barski, Jarosław Jerzy; Obuchowicz, Ewa; Małecki, Andrzej

2017-11-01

The study aimed to test the hypotheses that chronic social instability stress (CSIS) alters behavioral and physiological parameters and expression of selected genes important for stress response and social behaviors. Adult female Sprague-Dawley rats were subjected to the 4-week CSIS procedure, which involves unpredictable rotation between phases of isolation and overcrowding. Behavioral analyses (Experiment 1) were performed on the same rats before and after CSIS (n = 16) and physiological and biochemical measurements (Experiment 2) were made on further control (CON; n = 7) and stressed groups (CSIS; n = 8). Behaviors in the open field test (locomotor and exploratory activities) and elevated-plus maze (anxiety-related behaviors) indicated anxiety after CSIS. CSIS did not alter the physiological parameters measured, i.e. body weight gain, regularity of estrous cycles, and circulating concentrations of stress hormones and sex steroids. QRT-PCR analysis of mRNA expression levels was performed on amygdala, hippocampus, prefrontal cortex (PFC), and hypothalamus. The main finding is that CSIS alters the mRNA levels for the studied genes in a region-specific manner. Hence, expression of POMC (pro-opiomelanocortin), AVPR1a (arginine vasopressin receptor), and OXTR (oxytocin receptor) significantly increased in the amygdala following CSIS, while in PFC and/or hypothalamus, POMC, AVPR1a, AVPR1b, OXTR, and ERβ (estrogen receptor beta) expression decreased. CSIS significantly reduced expression of CRH-R1 (corticotropin-releasing hormone receptor type 1) in the hippocampus. The directions of change in gene expression and the genes and regions affected indicate a molecular basis for the behavior changes. In conclusion, CSIS may be valuable for further analyzing the neurobiology of stress-related disorders in females.

Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

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Oosthuizen, M K; Amrein, I

2016-06-02

Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

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Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

2014-06-01

Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

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Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

2008-02-01

Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.

Science.gov (United States)

Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J; Bueno, Susan M; Gonzalez, Pablo A; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M; Riedel, Claudia A

2012-09-01

Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF.

Pavlovian autoshaping procedures increase plasma corticosterone and levels of norepinephrine and serotonin in prefrontal cortex in rats.

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Tomie, Arthur; Tirado, Aidaluz D; Yu, Lung; Pohorecky, Larissa A

2004-08-12

Pavlovian autoshaping procedures provide for pairings of a small object conditioned stimulus (CS) with a rewarding substance unconditioned stimulus (US), resulting in the acquisition of complex sequences of CS-directed skeletal-motor responses or autoshaping conditioned responses (CRs). Autoshaping procedures induce higher post-session levels of corticosterone than in controls receiving CS and US randomly, and the enhanced post-session corticosterone levels have been attributed to the appetitive or arousal-inducing effects of autoshaping procedures. Enhanced corticosterone release can be induced by aversive stimulation or stressful situations, where it is often accompanied by higher levels of norepinephrine (NE) and serotonin (5-HT) in prefrontal cortex (PFC) but not in striatum (ST). Effects of autoshaping procedures on post-session corticosterone levels, NE contents in PFC, and 5-HT contents in PFC and ST were investigated in male Long-Evans rats. Post-session blood samples revealed higher corticosterone levels in the CS-US Paired group (n = 46) than in the CS-US Random control group (n = 21), and brain samples revealed higher levels of PFC NE and 5-HT in CS-US Paired group. Striatal 5-HT levels were unaltered by the autoshaping procedures. Autoshaping procedures provide for appetitive stimulation and induce an arousal-like state, as well as simultaneous stress-like changes in plasma corticosterone and monoamine levels in PFC. Autoshaping, therefore, may be useful for the study of endocrine and central processes associated with appetitive conditions.

A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat.

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Maïte Hotte

Full Text Available BACKGROUND: We aimed to further understand the relationship between cAMP concentration and mnesic performance. METHODS AND FINDINGS: Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p., rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p. and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p. before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold, prefrontal (1.3 fold and perirhinal (1.3 fold cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold from drug-treated rats (except for milrinone+RS 67333 treatment. After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold and the perirhinal cortex (2.1 fold from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold and milrinone (respectively 1.46 fold and 1.56 fold-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h. CONCLUSIONS: Our results strongly suggest that a "pre-sample" early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.

Percutaneous absorption of triadimefon in the adult and young male and female rat

International Nuclear Information System (INIS)

Knaak, J.B.; Yee, K.; Ackerman, C.R.; Zweig, G.; Wilson, B.W.

1984-01-01

The percutaneous absorption of 14 C-phenoxy ring labeled triadimefon was studied in adult and young male and female Sprague-Dawley rats. Triadimefon was applied (41.1 to 46.4 micrograms/cm2) in 0.2 ml of acetone to areas comprising 3% of the body surface (7.0 to 14.5 cm2). Thirty-six animals were treated at the initiation of each study. Groups of three animals were subsequently killed at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hr after treatment. Skin from the treated area as well as blood, heart, liver, kidneys, remaining carcass, urine, and feces were analyzed for 14 C by scintillation counting techniques. Based on 14 C counts, triadimefon was lost more rapidly from the skin of young animals (t 1/2, 20 to 25 hr) than from the skin of adult animals (t 1/2, 29 to 53 hr). Recovery studies indicated that adult males, adult females, young males, and young females, respectively, absorbed 53, 82, 57, and 52% of the dose. The rest of the dose based on material balance was presumably lost by evaporation. Approximately 2.5 to 3.9% of the dose penetrated the skin in one hour and was available for absorption. The rate of entry triadimefon into blood was 2 to 2.5 times faster for young than that observed in adult animals. Elimination of it from blood was faster in the case of the young animals. Triadimefon was absorbed through the skins of the adult male, adult female, young male, and young female rats, respectively, at rates of 0.20, 0.50, 0.58, and 0.48 micrograms/hr/cm2 of skin

SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

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Lim, S-I; Yoo, C-H; Song, K-H; Choe, B-Y; Woo, D-C

2016-01-01

Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

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Lim, S-I; Yoo, C-H [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of)

2016-06-15

Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

Medial prefrontal cortex activation facilitates re-extinction of fear in rats

OpenAIRE

Chang, Chun-hui; Maren, Stephen

2011-01-01

It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training. Immediately prior to extinction, rats received microinfusions into the IL of the GABAA receptor antagonist, picrotoxin, or the NMDA receptor partia...

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

Science.gov (United States)

Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

2016-08-10

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes

CHRONIC ALCOHOLISM ON THE SEMINAL VESICLE AND TESTIS WEIGHT OF ADULT RATS (Rattus norvegicus)

OpenAIRE

Martinez, F. E.; Martinez, M.; Cagnon, V. H. A.; Mello Junior, W.; Padovani, C. R.; Garcia, P. J.

1997-01-01

Effects of experimental chronic alcoholism on the accessory sexual glands weight and testes weight were studied. Male adult albino rats received only sugar cane brandy at 30 Gay Lussac (v/v), while the controls received tap water. After periods of 60, 120, 180 and 240 days, rats from each group were anesthetized, weighed and sacrificed. Alterations in mean daily solid food intake and liquid, mean daily weight gain, mean prostate weight, mean seminal vesicle and coagulating gland weights and t...

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders.

Science.gov (United States)

Aoki, Y; Abe, O; Yahata, N; Kuwabara, H; Natsubori, T; Iwashiro, N; Takano, Y; Inoue, H; Kawakubo, Y; Gonoi, W; Sasaki, H; Murakami, M; Katsura, M; Nippashi, Y; Takao, H; Kunimatsu, A; Matsuzaki, H; Tsuchiya, K J; Kato, N; Kasai, K; Yamasue, H

2012-10-23

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.

Early-stage attenuation of phase-amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of Alzheimer's disease.

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Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

2018-03-01

Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of gamma-aminobutyric acid-ergic signaling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABA A ) receptor subunits α1 , α5, and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is part of the Special Issue "Vascular Dementia". © 2017 Her Majesty the Queen in Right of Canada Journal of Neurochemistry © 2017 International Society for Neurochemistry.

Compensatory Processing During Rule-Based Category Learning in Older Adults

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Bharani, Krishna L.; Paller, Ken A.; Reber, Paul J.; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G.

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex. PMID:26422522

The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

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Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

2016-05-01

The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory. © 2015 Wiley Periodicals, Inc.

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

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Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury.

Science.gov (United States)

Smith, H K; Plyley, M J; Rodgers, C D; McKee, N H

1999-07-01

The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

The Blockade of Glutamate N-methyl-D-aspartate Receptors into the Prelimbic of Prefrontal Cortex Decreases Morphine-induced Conditioned Place Preference in Rat

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Samad Javadi

2017-12-01

Full Text Available BACKGROUND: The prelimbic area (PL of the prefrontal cortex is susceptible to abnormal developmental stimuli that raises the risk of addiction. Glutamate receptors play a key role in opiate reinforcement and reward functions in this area. Therefore, we examined the effect of the DL-2-amino-5-phosphonopentanoic acid (AP5, as N-methyl-D-aspartate (NMDA receptor antagonist into the PL on the phases of conditioned place preference (CPP induced by morphine. METHODS: Male Wistar rats were divided into 12 groups (3 surgical groups for each dose of morphine in any phase of CPP and anaesthetized with chloral hydrate. Cannula was implanted into the PL and the AP5 was injected into this area and morphine-induced CPP was investigated. Data were processed with the commercially available SPSS 22 software using one-way ANOVA and Tukey's test. p<0.05 were considered statistically significant. RESULTS: Our findings indicated, morphine in doses of 2.5 to 10 mg/kg induced CPP. Microinjection of various doses of the AP5 into the PL before the administration of the effective dose of morphine significantly reduced place preference in the acquisition and the expression phases of the CPP test compared to the sham group (p<0.001. In another set of our experiments was seen that, different doses of the AP5 with the ineffective dose of morphine only reduced the expression phase of the CPP (p<0.001 while, produced neither preference nor aversion effect on the acquisition phase (p=0.147. CONCLUSION: It seems that the glutamate NMDA receptors in the PL through memory formation and morphine-related reward signals play a critical role in addiction process during morphine-induced CPP. KEYWORDS: N-methyl-aspartate, morphine, glutamate receptor, prefrontal cortex, reward

Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity for cognitive control.

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Schulz, Kurt P; Clerkin, Suzanne M; Newcorn, Jeffrey H; Halperin, Jeffrey M; Fan, Jin

2014-09-01

Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: Effects of novelty and handling and comparison to the nucleus accumbens

NARCIS (Netherlands)

Feenstra, M. G.; Botterblom, M. H.; Mastenbroek, S.

2000-01-01

We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the

Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

Science.gov (United States)

Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

2006-09-15

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

International Nuclear Information System (INIS)

Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

1988-01-01

The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

Effects of marijuana use on prefrontal and parietal volumes and cognition in emerging adults.

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Price, Jenessa S; McQueeny, Tim; Shollenbarger, Skyler; Browning, Erin L; Wieser, Jon; Lisdahl, Krista M

2015-08-01

Chronic marijuana (MJ) use among adolescents has been associated with structural and functional abnormalities, particularly in developing regions responsible for higher order cognition. This study investigated prefrontal (PFC) and parietal volumes and executive function in emerging adult MJ users and explored potential gender differences. Participants (ages 18-25) were 27 MJ users and 32 controls without neurologic or psychiatric disorders or heavy other drug use. A series of multiple regressions examined whether group status, past year MJ use, and their interactions with gender predicted ROI volumes. Post hoc analyses consisted of brain-behavior correlations between volumes and cognitive variables and Fisher's z tests to assess group differences. MJ users demonstrated significantly smaller medial orbitofrontal (mOFC; p = 0.004, FDR p = 0.024) and inferior parietal volumes (p = 0.04, FDR p = 0.12); follow-up regressions found that increased past year MJ use did not significantly dose-dependently predict smaller mOFC volume in a sub-sample of individuals with at least one past year MJ use. There were no significant gender interactions. There was a significant brain-behavior difference by group, such that smaller mOFC volumes were associated with poorer complex attention for MJ users (p < 0.05). Smaller mOFC volumes among MJ users suggest disruption of typical neurodevelopmental processes associated with regular MJ use for both genders. These results highlight the need for longitudinal, multi-modal imaging studies providing clearer information on timing of neurodevelopmental processes and neurocognitive impacts of youth MJ initiation.

The flexible use of multiple cue relationships in spatial navigation : A comparison of water maze performance following hippocampal, medial septal, prefrontal cortex, or posterior parietal cortex lesions

NARCIS (Netherlands)

Compton, DM; Griffith, HR; McDaniel, WF; Foster, RA; Davis, BK

Rats prepared with lesions of the prefrontal cortex, posterior parietal cortex, hippocampus, or medial septal area were tested for acquisition of a number of variations of the open-field water maze using a version of place learning assessment described by Eichenbaum, Stewart, and Morris (1991).

Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

DEFF Research Database (Denmark)

Henningsen, Kim; Johannesen, Mads Dyrvig; Bouzinova, Elena

2012-01-01

In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats.

Science.gov (United States)

Alaverdashvili, Mariam; Li, Xue; Paterson, Phyllis G

2015-11-01

Adult protein-energy malnutrition (PEM) often occurs in combination with neurological disorders affecting hand use and walking ability. The independent effects of PEM on motor function are not well characterized and may be obscured by these comorbidities. Our goal was to undertake a comprehensive evaluation of sensorimotor function with the onset and progression of PEM in an adult male rat model. In Expt. 1 and Expt. 2, male Sprague-Dawley rats (14-15 wk old) were assigned ad libitum access for 4 wk to normal-protein (NP) or low-protein (LP) diets containing 12.5% and 0.5% protein, respectively. Expt. 1 assessed muscle strength, balance, and skilled walking ability on days 2, 8, and 27 by bar-holding, cylinder, and horizontal ladder walking tasks, respectively. In addition to food intake and body weight, nutritional status was determined on days 3, 9, and 28 by serum acute-phase reactant and corticosterone concentrations and liver lipids. Expt. 2 addressed the effect of an LP diet on hindlimb muscle size. PEM evolved over time in rats consuming the LP diet. Total food intake decreased by 24% compared with the NP group. On day 28, body weight and serum albumin decreased by 31% and 26%, respectively, and serum α2-macroglobulin increased by 445% (P malnutrition. This model can be used in combination with disease models of sensorimotor deficits to examine the interactions between nutritional status, other treatments, and disease progression. © 2015 American Society for Nutrition.

Auditory Connections and Functions of Prefrontal Cortex

Directory of Open Access Journals (Sweden)

Bethany ePlakke

2014-07-01

Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

Auditory connections and functions of prefrontal cortex

Science.gov (United States)

Plakke, Bethany; Romanski, Lizabeth M.

2014-01-01

The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease.

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Wong, Emily M; Walby, William F; Wilson, Dennis W; Tablin, Fern; Schelegle, Edward S

2018-05-01

Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive (SH) Wistar-Kyoto rats. Conscious, mature adult male normal Wistar-Kyoto (NW) and SH rats were exposed to one of the following atmospheres: filtered air (FA); UFPM (∼ 250 μg/m3); O3 (1.0 ppm); or UFPM + O3 (∼ 250 μg/m3 + 1.0 ppm) combined for 6 h, followed by an 8 h FA recovery period. Lung sections were evaluated for lesions in the large airways, terminal bronchiolar/alveolar duct regions, alveolar parenchyma, and vasculature. NW and SH rats were similarly affected by the combined-pollutant exposure, displaying severe injury in both large and small airways. SH rats were particularly susceptible to O3 exposure, exhibiting increased injury scores in terminal bronchioles and epithelial degeneration in large airways. UFPM-exposure groups had minimal histologic changes. The chemical composition of UFPM was altered by the addition of O3, indicating that ozonolysis promoted compound degradation. O3 increased the biologic potency of UFPM, resulting in greater lung injury following exposure. Pathologic manifestations of CVD may confer susceptibility to air pollution by impairing normal lung defenses and responses to exposure.

Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.

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Gruene, Tina M; Roberts, Elian; Thomas, Virginia; Ronzio, Ashley; Shansky, Rebecca M

2015-08-01

The neural projections from the infralimbic region of the prefrontal cortex to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphologic characteristics of these neurons and successful extinction in male and female subjects is unknown. Using classic cued fear conditioning and an extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We combined retrograde tracing with fluorescent intracellular microinjections to perform three-dimensional reconstructions of infralimbic neurons that project to the basolateral amygdala in these groups. The HF and LF male rats exhibited neuroanatomical distinctions that were not observed in HF or LF female rats. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF and LF phenotypes emerged in male rats during extinction and in female rats during fear conditioning, which does not involve infralimbic-basolateral amygdala neurons. Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are relevant not only to future basic research on sex differences in fear conditioning and extinction but also to exposure-based clinical therapies, which are similar in premise to fear extinction and which are primarily used to treat disorders that are more common in women than in men. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Memory retrieval in response to partial cues requires NMDA receptor-dependent neurotransmission in the medial prefrontal cortex.

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Jo, Yong Sang; Choi, June-Seek

2014-03-01

The medial prefrontal cortex (mPFC) has been suggested to play a crucial role in retrieving detailed contextual information about a previous learning episode in response to a single retrieval cue. However, few studies investigated the neurochemical mechanisms that mediate the prefrontal retrieval process. In the current study, we examined whether N-methyl-D-aspartate receptors (NMDARs) in the mPFC were necessary for retrieval of a well-learned spatial location on the basis of partial or degraded spatial cues. Rats were initially trained to find a hidden platform in the Morris water maze using four extramaze cues in the surrounding environment. Their retrieval performance was subsequently tested under different cue conditions. Infusions of DL-2-amino-5-phosphonovaleric acid (APV), a NMDAR antagonist, significantly disrupted memory retrieval when three of the original cues were removed. By contrast, APV injections into the mPFC did not affect animals' retrieval performance when the original cues were presented or when three novels landmarks were added alongside the original cues. These results indicate that prefrontal NMDARs are required for memory retrieval when allocentric spatial information is degraded. NMDAR-dependent neurotransmission in the mPFC may facilitate an active retrieval process to reactivate complete contextual representations associated with partial retrieval cues. Copyright © 2013 Elsevier Inc. All rights reserved.

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

Science.gov (United States)

Chang, Chun-Hui

2017-07-01

The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017

Chronic social isolation suppresses proplastic response and promotes proapoptotic signalling in prefrontal cortex of Wistar rats.

Science.gov (United States)

Djordjevic, Ana; Adzic, Miroslav; Djordjevic, Jelena; Radojcic, Marija B

2010-08-15

Successful adaptation to stress involves synergized actions of glucocorticoids and catecholamines at several levels of the CNS, including the prefrontal cortex (PFC). Inside the PFC, hormonal signals trigger concerted actions of transcriptional factors, such as glucocorticoid receptor (GR) and nuclear factor kappa B (NFkappaB), culminating in a balanced, proadaptive expression of their common genes, such as proplastic NCAM and/or apoptotic Bax and Bcl-2. In the present study, we hypothesized that chronic stress may compromise the balance between GR and NFkappaB signals and lead to an altered/maladaptive expression of their cognate genes in the PFC. Our results obtained with Wistar rats exposed to chronic social isolation indicated alterations of the GR relative to the NFkappaB, in favor of the GR, in both the cytoplasmic and the nuclear compartments of the PFC. Although these alterations did not affect the induction of proplastic NCAM gene, they decreased the NCAM sialylation necessary for plastic response and caused marked relocation of the mitochondrial membrane antiapoptotic Bcl-2 protein to its cytoplasmic form. Moreover, the compromised PSA-NCAM plastic response found under chronic stress was sustained after exposure of animals to the subsequent acute stress, whereas the proapoptotic signals were further emphasized. It is concluded that chronic social isolation of Wistar animals leads to a maladaptive response of the PFC, considering the diminishment of its plastic potential and potentiating of apoptosis. Such conditions in the PFC are likely to compromise its ability to interact with other CNS structures, such as the hippocampus, which is necessary for successful adaptation to stress. (c) 2010 Wiley-Liss, Inc.

Effects of thiamine deficiency on food intake and body weight increment in adult female and growing rats.

Science.gov (United States)

Bâ, Abdoulaye

2012-09-01

The present study compared the effects of thiamine (vitamin B1) deficiency (TD) on the patterns of food intake and body weight in adult female and neonatal Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine (210 B1). TD led to a marked reduction in food intake and the body weight set point, both recovering rapidly to their initial level in only 3 days after dietetic reversion. The effects of TD in developing rats were evaluated by subjecting pregnant rats to thiamine restriction during different time windows: prenatal (3 days before mating to parturition); perinatal (7 days after mating to the 10th postnatal day); and postnatal (from parturition to weaning). The effect of TD on the occurrence of low birth weight and ponderal growth retardation was examined from postnatal days 1 to 45. Only perinatal TD significantly decreased birth weight relative to untreated or pair-fed controls. Moreover, compared with the control treatments, ponderal growth retardation was not induced by prenatal TD, whereas induction of TD from perinatal into postnatal periods did cause ponderal growth retardation, with long-lasting effects persisting in adulthood. The results suggest a major physiological role of thiamine in the homeostasis of body weight programming, increment, and set point regulation in both offspring and adult female rats.

Peripubertal castration of male rats, adult open field ambulation and partner preference behavior.

Science.gov (United States)

Brand, T; Slob, A K

1988-09-15

The validity of the hypothesis put forward earlier, that testicular secretions during puberty have an organizing effect on open field ambulation was examined. Male rats were castrated or sham-operated at days 21, 43 or 70. At the age of 17 weeks the males were tested in an automated, octagonal open field (3 consecutive days, 3 min/day) for locomotor activity. Male rats castrated at day 21 or day 43 ambulated more than sham-castrated controls. Males castrated at day 70 did not differ from sham-castrated controls. It thus appears that pubertal testicular secretion(s) organize adult open field locomotor activity in male rats. From 18 weeks of age partner preference behavior was tested in the same open field apparatus with one adjacent cage containing an ovariectomized female and an opposite one containing an ovariectomized female brought into heat. The females in the adjacent cages were separated from the experimental males in the octagonal cage by wire mesh. Peripubertally castrated males did not show a clear-cut partner preference, whereas the intact males preferred the vicinity of the estrous female. There were no differences among the males castrated either before, during or after puberty. Testosterone treatment (crystalline T in silastic capsules) caused peripubertally castrated males to prefer the estrous female. Thus, adult partner preference behavior does not seem to be organized by peripubertal testicular androgens.

Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia

DEFF Research Database (Denmark)

Fabricius, Katrine; Steiniger-Brach, Björn; Helboe, Lone

2011-01-01

Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include...... dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared...

Role of medial prefrontal cortex serotonin 2A receptors in the control of retrieval of recognition memory in rats.

Science.gov (United States)

Bekinschtein, Pedro; Renner, Maria Constanza; Gonzalez, Maria Carolina; Weisstaub, Noelia

2013-10-02

Often, retrieval cues are not uniquely related to one specific memory, which could lead to memory interference. Controlling interference is particularly important during episodic memory retrieval or when remembering specific events in a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC) in episodic memory in human studies, information regarding the mechanisms and neurotransmitter systems in PFC involved in memory is scarce. Although the serotoninergic system has been linked to PFC functionality and modulation, its role in memory processing is poorly understood. We hypothesized that the serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could have a role in the control of memory retrieval. In this work we used different versions of the object recognition task in rats to study the role of the serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory in a spontaneous novelty preference task, while sparing single-item recognition memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal-mPFC interaction during retrieval of this type of memory, suggesting that the mPFC controls the expression of memory traces stored in the hippocampus biasing retrieval to the most relevant one.

Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

Science.gov (United States)

Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

2018-07-02

Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of the effects of a prenatal or postnatal irradiation of 150 rads in adult rats

International Nuclear Information System (INIS)

Coffigny, H.; Pasquier, C.

Pregnant females and newborn rats were exposed to a gamma irradiation of 150 rads. The stage of gestation at the time of irradiation varied from 14 to 21 days. The newborn rats were irradiated at 0, 1 and 2 days of age. The effect of irradiation of foetus and newborn rats depends on the age of the animal at the time of irradiation. This effect was specially important at the beginning of the foetal life. Neonatal mortality, growth of body weight and adult brain development were investigated. A modification of germ cell radiosensitivity during the period studied, was emphasized [fr

Adult and newborn rat inner retinal oxygenation during carbogen and 100% oxygen breathing. Comparison using magnetic resonance imaging delta Po2 mapping.

Science.gov (United States)

Berkowitz, B A

1996-09-01

To test the hypothesis that breathing carbogen (95% O2-5% CO2) oxygenates the inner retina better than breathing 100% oxygen using an magnetic resonance imaging (MRI) method that noninvasively measures inner retinal oxygenation in normal adult and newborn rats. Urethane-anesthetized adult and newborn (day 18) rats were studied. Sequential images were acquired in room air combined with either 100% oxygen or carbogen breathing. Normalized vitreous signal intensity changes were converted to oxygen tension changes (delta PO2) either on a pixel-by-pixel basis or in specific regions of interest. Systemic levels of hyperoxia during carbogen or 100% oxygen breathing were not significantly different (P > 0.05). In the adult rat, a significant difference (P = 0.017) was found in the preretinal vitreous delta PO2 during the breathing of either carbogen (130 +/- 9 mm Hg, mean +/- SEM; n = 5) or 100% oxygen (88 +/- 16 mm Hg; n = 5). Agreement was found between the MRI-determined delta PO2 values and literature oxygen microelectrodes data. In the newborn rat, significant differences (P delta PO2 were found during carbogen (164 +/- 23 mm Hg; n = 3) and oxygen breathing (91 +/- 8 mm Hg; n = 3). MRI delta PO2 mapping demonstrated for the first time that in the normal adult and newborn rat eye, carbogen breathing oxygenates the inner retina better than 100% oxygen breathing.

Changes of heart rate variability and prefrontal oxygenation during Tai Chi practice versus arm ergometer cycling.

Science.gov (United States)

Lu, Xi; Hui-Chan, Christina Wan-Ying; Tsang, William Wai-Nam

2016-11-01

[Purpose] Exercise has been shown to improve cardiovascular fitness and cognitive function. Whether the inclusion of mind over exercise would increase parasympathetic control of the heart and brain activities more than general exercise at a similar intensity is not known. The aim of this study was to compare the effects of Tai Chi (mind-body exercise) versus arm ergometer cycling (body-focused exercise) on the heart rate variability and prefrontal oxygenation level. [Subjects and Methods] A Tai Chi master was invited to perform Tai Chi and arm ergometer cycling with similar exercise intensity on two separate days. Heart rate variability and prefrontal oxyhemoglobin levels were measured continuously by a RR recorder and near-infrared spectroscopy, respectively. [Results] During Tai Chi exercise, spectral analysis of heart rate variability demonstrated a higher high-frequency power as well as a lower low-frequency/high-frequency ratio than during ergometer cycling, suggesting increased parasympathetic and decreased sympathetic control of the heart. Also, prefrontal oxyhemoglobin and total hemoglobin levels were higher than those during arm ergometer exercise. [Conclusion] These findings suggest that increased parasympathetic control of the heart and prefrontal activities may be associated with Tai Chi practice. Having a "mind" component in Tai Chi could be more beneficial for older adults' cardiac health and cognitive function than body-focused ergometer cycling.

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

Science.gov (United States)

Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

2013-03-01

Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

Data.gov (United States)

U.S. Environmental Protection Agency — behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological...

Effects of chronic isoproterenol administration of β1-adrenoceptors and growth of pancreas of young and adult rats

International Nuclear Information System (INIS)

Schneyer, C.A.; Humphreys-Beher, M.

1988-01-01

[ 3 H]Dihydroalprenolol (DHA) binding of membranes of adult pancreas differed from that of pancreas of young rats, and the DHA binding in the presence of atenolol or butoxamine also was different in the two age groups. The adult pancreas had 93% β 2 - and 7% β 1 -adrenoceptors and did not exhibit an increased incorporation of [ 3 H]thymidine into deoxyribonucleic acid (DNA) following 2 days of DL-isoproterenol (ISO) administration; in contrast, pancreas of the 20-day-old rat had 71% β 2 -adrenoceptors and 27% β 1 -adrenoceptors and exhibited a 34-fold increase over that of adult, and a 6-fold increase over that of the control 20-day-old pancreas. Acinar cell differentiation was also accelerated by a 7-day regimen of ISO administration from 13 to 20 days of age. These growth responses to ISO appear to be β 1 mediated. The lack of β 1 -adrenoceptors in the adult may account for the failure of the adult pancreas to exhibit a growth response to ISO

The Cortical Connectivity of the Prefrontal Cortex in the Monkey Brain

Science.gov (United States)

Yeterian, Edward H.; Pandya, Deepak N.; Tomaiuolo, Francesco; Petrides, Michael

2011-01-01

One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and, on the other hand, with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal

Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

Science.gov (United States)

Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

2017-04-01

Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

Neonatal stress tempers vulnerability of acute stress response in adult socially isolated rats

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Mariangela Serra

2014-06-01

Full Text Available Adverse experiences occurred in early life and especially during childhood and adolescence can have negative impact on behavior later in life and the quality of maternal care is considered a critical moment that can considerably influence the development and the stress responsiveness in offspring. This review will assess how the association between neonatal and adolescence stressful experiences such as maternal separation and social isolation, at weaning, may influence the stress responsiveness and brain plasticity in adult rats. Three hours of separation from the pups (3-14 postnatal days significantly increased frequencies of maternal arched-back nursing and licking-grooming by dams across the first 14 days postpartum and induced a long-lasting increase in their blood levels of corticosterone. Maternal separation, which per sedid not modified brain and plasma allopregnanolone and corticosterone levels in adult rats, significantly reduced social isolation-induced decrease of the levels of these hormones. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were exposed to maternal separation was markedly reduced respect to that observed in socially isolated animals. Our results suggest that in rats a daily brief separation from the mother during the first weeks of life, which per se did not substantially alter adult function and reactivity of hypothalamic-pituitary-adrenal (HPA axis, elicited a significant protection versus the subsequent long-term stressful experience such that induced by social isolation from weaning. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in NeonatologyGuest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

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Mabrouk, Aymen; Ben Cheikh, Hassen

2016-06-01

This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication. © The Author(s) 2014.

Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia.

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Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Di Giorgio, Annabella; Caforio, Grazia; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Attrotto, Maria Teresa; Colagiorgio, Lucia; Todarello, Giovanna; Piva, Francesco; Papazacharias, Apostolos; Masellis, Rita; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Rampino, Antonio; Quarto, Tiziana; Giulietti, Matteo; Lipska, Barbara K; Kleinman, Joel E; Popolizio, Teresa; Weinberger, Daniel R; Usiello, Alessandro; Bertolino, Alessandro

2013-08-01

OBJECTIVE Glycogen synthase kinase 3β (GSK-3β) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3β gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3β functional variation with 1) GSK-3β mRNA expression from postmortem prefrontal cortex, 2) GSK-3β and β-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3β (rs12630592) was associated with reduced GSK-3β mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3β protein expression and kinase activity, as well as with downstream effects on β-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3β variation is implicated in multiple phenotypes relevant to schizophrenia.

Sex-Specific Skeletal Muscle Fatigability and Decreased Mitochondrial Oxidative Capacity in Adult Rats Exposed to Postnatal Hyperoxia

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Laura H. Tetri

2018-03-01

Full Text Available Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.

Chronic Fluoxetine Treatment Upregulates the Activity of the ERK1/2-NF-κB Signaling Pathway in the Hippocampus and Prefrontal Cortex of Rats Exposed to Forced-Swimming Stress.

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Cui, Jingqiu; Yang, Kun; Yu, Xue; Wang, Jing-Lan; Li, Jie; Zhang, Yong; Li, Hengfen

2016-01-01

The aim of this study was to explore whether or not the antidepressant actions of fluoxetine (FLX) are correlated with extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor κ-light chain enhancer of activated B cells (NF-κB) in the hippocampus (HC) and prefrontal cortex (PFC) of rats. A total of 108 male Sprague-Dawley rats were randomly divided into 6 groups of 18 rats each. Group 1 was the control group, while group 2 comprised the depressed model in which rats were subjected to 28 days of forced-swimming stress (FST); groups 3-6 were also subjected to 28 days of FST and treated with FLX once a day for 1 day (group 3; F1d), 1 week (group 4; F1w), 2 weeks (group 5; F2w), or 4 weeks (group 6; F4w). The control group was not subjected to FST or treated with FLX. Behavior tests that included the Morris water maze (MWM) and saccharin preference were performed, and ERK1/2 and NF-κB proteins were assayed using Western blot. The rats in the control group and in groups 5 and 6 (F2w and F4w, respectively) had a significantly shorter average escape latency, needed more attempts in order to successfully cross the platform, and had a greater saccharin preference than those in the depressed group (p < 0.05). In the depressed group, the phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated NF-κB (p-NF-κB) expression in the HC and PFC were lower than in the control group (p < 0.05). Treatment with FLX reversed the changes in the expression of p-ERK1/2 and p-NF-κB in rats in the F2w and F4w groups. In this study, FLX treatment for 2 weeks or longer reversed the impaired spatial learning, memory, and anhedonia observed in the depressed model rats and upregulated the activities of the ERK1/2-NF-κB signaling pathway. © 2016 S. Karger AG, Basel.

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

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Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M

2014-04-01

Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

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S Mojtahedi

2014-08-01

Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

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Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

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Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

2015-09-14

Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

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Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

Strengthening of Existing Episodic Memories Through Non-invasive Stimulation of Prefrontal Cortex in Older Adults with Subjective Memory Complaints

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Rosa Manenti

2017-12-01

Full Text Available Episodic memory is critical to daily life functioning. This type of declarative memory declines with age and is the earliest cognitive function to be compromised in Alzheimer’s disease (AD. Subjective memory complaints are commonly reported by older adults and have been considered a risk factor for developing AD. The possibilities for prevention of memory disorders in older adults have increased substantially in recent years. Previous studies have shown that anodal transcranial Direct Current Stimulation (tDCS applied over the left lateral prefrontal cortex (PFC after a contextual reminder strengthened existing verbal episodic memories, conceivably through reconsolidation, in elderly people. In this study, we hypothesized that anodal tDCS applied over the left lateral PFC after a contextual reminder would improve delayed memory retrieval relative to placebo (sham stimulation in elderly individuals with SMC. Twenty-two subjects learned a list of words. Twenty-four hour later, tDCS (anodal or placebo was applied over the left lateral PFC after a contextual reminder. Memory retrieval was tested 48h and 30 days later. These findings showed that anodal tDCS over the left lateral PFC strengthened existing episodic memories, a behavioral effect documented by improved recognition up to 30 days, relative to placebo stimulation. This study suggests that tDCS after a contextual reminder can induce long-lasting beneficial effects by facilitating the consolidation processes and opens up the possibility to design specific non-invasive interventions aimed at preventing memory decline in this at-risk population.

Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

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Shahbazian, F.M.

1985-01-01

Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of [ 14 C]valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements

Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the infralimbic prefrontal cortex to the amygdala.

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David Frausto Peña

2014-09-01

Full Text Available Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations. Subjects with posttraumatic stress disorder (PTSD show impaired extinction of conditioned fear, which is associated with decreased ventromedial prefrontal cortex (vmPFC control over amygdala activity. Vagus nerve stimulation (VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here we investigated whether pairing VNS with extinction learning facilitates plasticity between the infralimbic (IL medial prefrontal cortex and the basolateral complex of the amygdala (BLA. Rats were trained on an auditory fear conditioning task, which was followed by a retention test and one day of extinction training. Vagus nerve stimulation or sham-stimulation was administered concurrently with exposure to the fear-conditioned stimulus and retention of fear conditioning was tested again 24 hours later. VNS-treated rats demonstrated a significant reduction in freezing after a single extinction training session similar to animals that received 5x the number of extinction pairings. To study plasticity in the IL-BLA pathway, we recorded evoked field potentials in the BLA in anesthetized animals 24 h after retention testing. Brief burst stimulation in the IL produced LTD in the BLA field response in fear-conditioned and sham-treated animals. In contrast, the same stimulation resulted in potentiation of the IL-BLA pathway in the VNS-treated group. The present findings suggest that VNS promotes plasticity in the IL-BLA pathway to facilitate extinction of conditioned fear responses.

Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.

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Montes, Pedro; Ruiz-Sánchez, Elizabeth; Calvillo, Minerva; Rojas, Patricia

2016-09-01

Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

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Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake

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Perry, Jennifer L.; Anderson, Marissa M.; Nelson, Sarah E.; Carroll, Marilyn E.

2007-01-01