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?FosB in the nucleus accumbens is critical for reinforcing effects of sexual reward.

ABSTRACT: Sexual behavior in male rats is rewarding and reinforcing. However, little is known about the specific cellular and molecular mechanisms mediating sexual reward or the reinforcing effects of reward on subsequent expression of sexual behavior. This study tests the hypothesis that ?FosB, the stably expressed truncated form of FosB, plays a critical role in the reinforcement of sexual behavior and experience-induced facilitation of sexual motivation and performance. Sexual experience was shown to cause ?FosB accumulation in several limbic brain regions including the nucleus accumbens (NAc), medial prefrontal cortex, ventral tegmental area and caudate putamen but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of ?FosB, was measured in sexually experienced and naïve animals. The number of mating-induced c-Fos-immunoreactive cells was significantly decreased in sexually experienced animals compared with sexually naïve controls. Finally, ?FosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with ?FosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of ?JunD, a dominant negative binding partner of ?FosB, attenuated sexual experience-induced facilitation of sexual performance and stunted long-term maintenance of facilitation compared to green fluorescence protein and ?FosB overexpressing groups. Together, these findings support a critical role for ?FosB expression in the NAc for the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance.

SUBMITTER: Pitchers KK

PROVIDER: S-EPMC2970635 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward.

Pitchers K K KK Frohmader K S KS Vialou V V Mouzon E E Nestler E J EJ Lehman M N MN Coolen L M LM

Genes, brain, and behavior 20100816 7

Sexual behavior in male rats is rewarding and reinforcing. However, little is known about the specific cellular and molecular mechanisms mediating sexual reward or the reinforcing effects of reward on subsequent expression of sexual behavior. This study tests the hypothesis that ΔFosB, the stably expressed truncated form of FosB, plays a critical role in the reinforcement of sexual behavior and experience-induced facilitation of sexual motivation and performance. Sexual experience was shown to c ...[more]

PMID: 20618447

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Project description:Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is a potential remedial therapy for drug craving and relapse, but the mechanism is poorly understood. We investigated changes in neurotransmitter levels during high frequency stimulation (HFS) of the unilateral NAc on morphine-induced rats. Sixty adult Wistar rats were randomized into five groups: the control group (administration of saline), the morphine-only group (systematic administration of morphine without electrode implantation), the morphine-sham-stimulation group (systematic administration of morphine with electrode implantation but not given stimulation), the morphine-stimulation group (systematic administration of morphine with electrode implantation and stimulation) and the saline-stimulation group (administration of saline with electrode implantation and stimulation). The stimulation electrode was stereotaxically implanted into the core of unilateral NAc and microdialysis probes were unilaterally lowered into the ipsilateral ventral tegmental area (VTA), NAc, and ventral pallidum (VP). Samples from microdialysis probes in the ipsilateral VTA, NAc, and VP were analyzed for glutamate (Glu) and ?-aminobutyric acid (GABA) by high-performance liquid chromatography (HPLC). The levels of Glu were increased in the ipsilateral NAc and VP of morphine-only group versus control group, whereas Glu levels were not significantly changed in the ipsilateral VTA. Furthermore, the levels of GABA decreased significantly in the ipsilateral NAc, VP, and VTA of morphine-only group when compared with control group. The profiles of increased Glu and reduced GABA in morphine-induced rats suggest that the presence of increased excitatory neurotransmission in these brain regions. The concentrations of the Glu significantly decreased while the levels of GABA increased in ipsilateral VTA, NAc, and VP in the morphine-stimulation group compared with the morphine-only group. No significant changes were seen in the morphine-sham stimulation group compared with the morphine-only group. These findings indicated that unilateral NAc stimulation inhibits the morphine-induced rats associated hyperactivation of excitatory neurotransmission in the mesocorticolimbic reward circuit.

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?FosB in the nucleus accumbens is critical for reinforcing effects of sexual reward.

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ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward.

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