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

To determine the role of dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) core in cocaine-induced behavioral sensitization, D2R antagonist, raclopride was bilaterally microinjected (2.5 or 5 nmol) into the NAc core of WT and D2R-/- mice and the initiation and expression phase of cocaine-mediated locomotor sensitization were analyzed. WT and D2R knockout (D2R-/-) mice received bilateral injections of either saline, or raclopride at the NAc core 30 min before each of five daily repeated injections of saline or cocaine (15 mg/kg i.p.). Following 2 weeks of withdrawal after repeated exposure to cocaine, the animals were pre-treated with an intra-accumbal injection of vehicle or raclopride before receiving a systemic cocaine challenge for the expression of sensitization. Animals which had been microinjected raclopride into NAc core displayed the enhancement of cocaine-induced behavioral response for the initiation but also for the expression of sensitization in WT as well as in D2R-/- mice, which was thus unaltered as compared to vehicle-injected control group. These results suggest that D2R in NAc core is not involved in cocaine-induced behavioral sensitization.
Animals ; Cocaine ; Dopamine ; Mice ; Microinjections ; Nucleus Accumbens ; Raclopride ; Receptors, Dopamine ; Receptors, Dopamine D2

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.
Animals ; Cannabinoids* ; Learning ; Membranes ; Memory ; Mice ; Motor Activity ; Neurons ; Nucleus Accumbens ; Traction ; Tremor

Sucrose and alcohol are rewarding and appetitive. They are occasionally over-consumed and cause addiction. The parabrachial nuclei (PbN) are the second taste relay in the central taste pathway. The nucleus accumbens (NAcc) is an important neural substrate in the reward system. Intake of sucrose or alcohol induces dopamine release in the NAcc. Although alcohol is not classified as a taste stimulus, a substantial number of sucrose-responsive neurons in the PbN respond to stimulation by alcohol on the tongue. In the present study, we investigated whether or not application of 0.5 M sucrose, 10% ethanol (EtOH), mixture of sucrose and EtOH, and double-distilled water (DDW) to the tongue induces c-Fos-like immunoreactivity (cFLI) in the PbN and NAcc. We also examined whether or not the number of cFLI following sucrose/EtOH is comparable to the number of cFLIs following sucrose and EtOH, respectively. Male Sprague-Dwaley rat was anesthetized with a mixture of Zoletil and Rompun while stimulation solution was applied to the anterior tongue. The rat was sacrificed by perfusion, and the fixed brain was sectioned and immunostained. Data from a total of 18 animals were analyzed. The number of cFLI following stimulation with sucrose and/or EtOH was greater than that of DDW in the PbN. Numbers of cFLI following sucrose, EtOH, and sucrose/EtOH were not significantly different from each other in the PbN. The number of cFLI in response to stimulation solution was not different from that of DDW in the NAcc. The result of the present study suggests that not only sucrose but also EtOH activates some neurons in the PbN, and that some pontine neurons possibly respond to both sucrose and EtOH.
Animals ; Brain ; Dopamine ; Ethanol ; Humans ; Male ; Neurons ; Nucleus Accumbens ; Perfusion ; Rats ; Reward ; Sucrose* ; Tongue ; Water ; Xylazine

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

BACKGROUNDOpiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens (NAc) in addiction. Deep brain stimulation (DBS) has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats.

METHODSA morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.

RESULTSHigh-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS ((268.25 ± 25.07) seconds) was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration ((303.29 ± 34.22) seconds). High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory.

CONCLUSIONBilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction.

Animals ; Electric Stimulation ; Male ; Morphine ; toxicity ; Morphine Dependence ; therapy ; Nucleus Accumbens ; metabolism ; Rats ; Rats, Sprague-Dawley

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Animals ; Dopaminergic Neurons/physiology* ; GABAergic Neurons/physiology* ; Mice ; Nucleus Accumbens/metabolism* ; Reward ; Ventral Tegmental Area/metabolism*