The nucleus accumbens (NAc) is the major component of the ventral striatum that regulates stress-induced depression. The NAc receives dopaminergic inputs from the ventral tegmental area (VTA), and the role of VTA-NAc neurons in stress response has been recently characterized. The NAc also receives glutamatergic inputs from various forebrain structures including the prelimbic cortex (PL), basolateral amygdala (BLA), and ventral hippocampus (vHIP), whereas the role of those glutamatergic afferents in stress response remains underscored. In the present study, we investigated the extent to which descending glutamatergic neurons activated by stress in the PL, BLA, and vHIP project to the NAc. To specifically label the input neurons into the NAc, fluorescent-tagged cholera toxin subunit B (CTB), which can be used as a retrograde neuronal tracer, was injected into the NAc. After two weeks, the mice were placed under restraint for 1 h. Subsequent histological analyses indicated that CTB-positive cells were detected in 170~680 cells/mm² in the PL, BLA, and vHIP, and those CTB-positive cells were mostly glutamatergic. In the PL, BLA, and vHIP regions analyzed, stress-induced c-Fos expression was found in 20~100 cells/mm². Among the CTB-positive cells, 2.6% in the PL, 4.2% in the BLA, and 1.1% in the vHIP were co-labeled by c-Fos, whereas among c-Fos-positive cells, 7.7% in the PL, 19.8% in the BLA, and 8.5% in the vHIP were co-labeled with CTB. These results suggest that the NAc receives a significant but differing proportion of glutamatergic inputs from the PL, BLA, and vHIP in stress response.
Animals ; Basolateral Nuclear Complex ; Cholera Toxin ; Depression ; Hippocampus ; Mice ; Neurons* ; Nucleus Accumbens* ; Prosencephalon ; Ventral Striatum ; Ventral Tegmental Area

The frontal cortex of rat is innervated by dopaminergic pathway(mesocortical pathway) arising from ventral tegmental area. Several studies have suggested that mesocortical dopaminergic neurons may modulate the function of dopaminergic neurons at subcortical sites. The effect of lesions of the dopaminergic nerve terminals in the medial prefrontal cortex of the rat on dopamine D1 and D2 receptors within the striatum and olfactory tubercle has been investigated. Bilateral 6-hydroxy-dopamine lesions were stereotaxically placed in the medial prefrontal cortex. Animal were pretreated with desipramine to block the uptake of neurotoxin into noradrenergic terminals and to make it more selective for dopamine terminal. After 2weeks later, we examined the changes of D1 and D2 receptors in caudate-putamen and nucleus accumbens by quantitative autoradiography using the specific D1 antagonist [3H]SCH23390 and D2 antagonist [3H]spiperone. The results shows that D1 receptor at striatum was up regulated 2weeks after destruction of dopamine terminals within medial prefrontal vortex of the rat. This findings suggest that frontal cortical dopamine system may regulate the dopamine system in corpus striatum.
Animals ; Autoradiography ; Corpus Striatum ; Desipramine ; Dopamine* ; Dopaminergic Neurons ; Nucleus Accumbens ; Olfactory Pathways ; Oxidopamine* ; Prefrontal Cortex* ; Rats* ; Receptors, Dopamine* ; Ventral Tegmental Area

OBJECTIVE: Prior functional magnetic resonance imaging (fMRI) work has revealed that children/adolescents with disruptive behavior disorders (DBDs) show dysfunctional reward/non-reward processing of non-social reinforcements in the context of instrumental learning tasks. Neural responsiveness to social reinforcements during instrumental learning, despite the importance of this for socialization, has not yet been previously investigated. METHODS: Twenty-nine healthy children/adolescents and 19 children/adolescents with DBDs performed the fMRI social/non-social reinforcement learning task. Participants responded to random fractal image stimuli and received social and non-social rewards/non-rewards according to their accuracy. RESULTS: Children/adolescents with DBDs showed significantly reduced responses within the caudate and posterior cingulate cortex (PCC) to non-social (financial) rewards and social non-rewards (the distress of others). Connectivity analyses revealed that children/adolescents with DBDs have decreased positive functional connectivity between the ventral striatum (VST) and the ventromedial prefrontal cortex (vmPFC) seeds and the lateral frontal cortex in response to reward relative to non-reward, irrespective of its sociality. In addition, they showed decreased positive connectivity between the vmPFC seed and the amygdala in response to non-reward relative to reward. CONCLUSION: These data indicate compromised reinforcement processing of both non-social rewards and social non-rewards in children/adolescents with DBDs within core regions for instrumental learning and reinforcement-based decision-making (caudate and PCC). In addition, children/adolescents with DBDs show dysfunctional interactions between the VST, vmPFC, and lateral frontal cortex in response to rewarded instrumental actions potentially reflecting disruptions in attention to rewarded stimuli.
Amygdala ; Attention Deficit and Disruptive Behavior Disorders ; Conditioning, Operant ; Fractals ; Frontal Lobe ; Gyrus Cinguli ; Learning ; Magnetic Resonance Imaging* ; Prefrontal Cortex ; Problem Behavior* ; Reinforcement, Social* ; Reward ; Socialization ; Ventral Striatum

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.
Adolescent ; Adult ; Animals ; Anxiety ; Aripiprazole ; Blotting, Western ; Cognition ; Dopamine ; Hippocampus ; Humans ; Locomotion ; Male ; Memory, Short-Term ; Models, Animal ; Prefrontal Cortex ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; Risperidone ; Synaptic Transmission ; Ventral Striatum

AIMTo investigate the changes in neuronal activities of the pedunculopontine nucleus (PPN) and the ventrolateral thalamic nucleus (VL) after unilateral 6-hydroxydopamin (6-OHDA) lesioning of the striatum in rats.

METHODSExtracellular single-unit recordings were perin normal rats and 6-OHDA lesioned rats to observe the firing rate and firing pattern occurring in PPN and VL neurons.

RESULTSThe firing rate of PPN neurones significantly increased from (8.31 +/- 0.62) Hz in normal rats to (10.70 +/- 0.85) Hz in 6-OHDA lesioned rats. The firing pattern changed towards more irregular and bursty when compared with the normal rats, with the firing rate increasing in regular pattern. The firing rate of VL neurones in normal rats and 6-OHDA lesioned rats were (6.25 +/- 0.54) Hz and (5.67 +/- 0.46)Hz respectively, whereas to normal animals. Surthere were no significant differences in these two groups. In addition, the firing pattern did not change in VL compared prisingly, the firing rate in burst pattern decreased significantly.

CONCLUSIONThese findings demonstrate that PPN neurons are overactive in 6-OHDAlesioned rats, indicating the participation of this nucleus in the pathophysiology of parkinsonism and the activities of VL neurons might be regulated by projection from PPN to VL.

Action Potentials ; physiology ; Animals ; Corpus Striatum ; physiopathology ; Male ; Neural Pathways ; injuries ; pathology ; physiopathology ; Neurons ; physiology ; Oxidopamine ; toxicity ; Parkinson Disease ; pathology ; physiopathology ; Pedunculopontine Tegmental Nucleus ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; injuries ; pathology ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology

No abstract available.
Animals ; Dopamine* ; Nucleus Accumbens* ; Panax* ; Rats* ; Saponins*

Paralimbic association area in the temporal pole is situated between sensory association areas and the limbic regions and has direct connections with these areas and the ventral striatum. Corticostriatal connections of paralimbic association area in the temporal pole were studied with particular emphasis on specific projections of the ventral striatum to identify different contributions to the functional outcome of the ventral striatum. Retrograde tracers were injected into the five different regions of the ventral striatum such as the ventromedial caudate nucleus, ventral shell, central shell, dorsal core of the nucleus accumbens (NA), and ventrolateral putamen to identify the labeled cells of origin. Present results indicate that the temporal pole has specifically dense projections to the ventral shell of NA. This differential pattern of corticostriatal connectivity suggests that ventral shell region of ventral striatum is preferentially involved in the convergence of sensory and limbic stimulus to motivational and emotional states.
Basal Ganglia ; Caudate Nucleus ; Nucleus Accumbens ; Primates* ; Putamen

OBJECTIVES: To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. METHODS: Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). RESULTS: (1) (-)-3-PPP had dual actions depending on the doses : at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater icrease ; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. CONCLUSIONS: These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.
Animals ; Dopamine* ; Haloperidol ; Limbic System ; Nucleus Accumbens* ; Rats*

The organization of the striatal projection fibers from the hippocampal formation (HF) was studied in the monkey with particular emphasis on specific projections of the ventral striatum. Retrograde tracers were injected into the five different regions of the ventral striatum such as the ventromedial caudate nucleus, ventral shell, central shell, and dorsal core of the nucleus accumbens (NA), and ventrolateral putamen. The ventromedial caudate nucleus and the shell of the NA received dense projections from the HF. Although the ventromedial caudate nucleus and the shell of the NA are both innervated by the HF, the shell receives the larger of these projections. This suggests that the HF is more strongly connected with the shell of the NA than with the ventromedial caudate nucleus. There are no differences between the ventral shell and central shell of the NA. Labeled neurons were mainly observed in the rostral parts of the dorsomedial CA1 and adjacent subicular complex (prosubiculum, subiculum, presubiculum, and parasubiculum) of the HF. These results suggest that the shell of the NA is the main converging site receiving hippocampal projections primarily related to integrating visuospatial and limbic information.
Basal Ganglia* ; Caudate Nucleus ; Haplorhini ; Hippocampus ; Neurons ; Nucleus Accumbens ; Primates* ; Putamen

OBJECTIVE: The purpose of our study was to measure and compare the c-fos mRNA expression patterns in the nucleus accumbens (NAS) and prefrontal cortex (PFC) of rats after the administration of haloperidol (2 mg/kg) or (-)-3-PPP (2 mg/kg) plus haloperidol (2 mg/kg). METHODS: Reverse transcriptase-polymerase chain reactions (RT-PCR) were performed on total RNA from samples of the NAS and PFC of rats to detect the expression of c-fos mRNA. As internal control, beta-actin mRNA was co-amplified. The products were separated by electrophoresis, and the density of bands was quantified using an image-analysis software. RESULTS: Both the administration of haloperidol (2 mg/kg) and (-)-3-PPP (2 mg/kg) plus haloperidol (2 mg/kg) increased the c-fos mRNA expression significantly (p<0.05) in the NAS, but had no effects in the PFC. In addition, the coadministration of (-)-3-PPP (2 mg/kg) and haloperidol (2 mg/kg) demonstrated more (0.05) remarkable c-fos mRNA expressions than those obtained with the administration of haloperidol (2 mg/kg) alone. CONCLUSION: These results suggest that the coadministration of (-)-3-PPP and haloperidol may have more potent antipsychotic effect compared to the administration of haloperidol alone.
Actins ; Animals ; Antipsychotic Agents ; Electrophoresis ; Haloperidol* ; Nucleus Accumbens* ; Prefrontal Cortex* ; Rats* ; RNA ; RNA, Messenger