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. 2010 Oct;9(7):831-40.
doi: 10.1111/j.1601-183X.2010.00621.x. Epub 2010 Aug 16.

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

K K Pitchers  1 , K S Frohmader, V Vialou, E Mouzon, E J Nestler, M N Lehman, L M Coolen
Affiliations

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

K K Pitchers et al. Genes Brain Behav. 2010 Oct.

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 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 cause ΔFosB 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 ΔFosB, 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, ΔFosB 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 ΔFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of ΔJunD, a dominant negative binding partner of ΔFosB, attenuated sexual experience-induced facilitation of sexual performance and stunted long-term maintenance of facilitation compared to green fluorescence protein and ΔFosB overexpressing groups. Together, these findings support a critical role for ΔFosB expression in the NAc for the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance.

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Figures

Figure 1
Figure 1
Representative images showing ΔFosB-IR cells (black) in the NAc of naïve no sex (A) and experience no sex (B) groups. aco: anterior commissure Scale bar indicates 100 µm.
Figure 2
Figure 2
Number of ΔFosB-IR cells in: A. infralimbic (IL), prelimbic (PL) and anterior cingulate cortex (ACA) subregions of the medial prefrontal cortex; B. Nucleus accumbens core and shell, and caudate putamen (CP); C. Rostral, middle, caudal and tail sections from the ventral tegmental area. Data are expressed as group means (± SEM). * indicates significant difference from sexually naïve animals (p=0.037-<0.001) (n=5 each group).
Figure 3
Figure 3
Representative images showing ΔFosB (green) and c-Fos (red) in NAc for each experimental group. Scale bar indicates 100 µm.
Figure 4
Figure 4
Sex experience-induced ΔFosB and mating-induced c-Fos. Numbers of ΔFosB (Core, A; Shell, C; ACA, E) or c-Fos (Core, B; Shell, D; ACA, F) immunoreactive cells for each group: NNS (n=5), NS (n=5), ENS (n=5) or ES (n=4). Data are expressed as group means (± SEM). * indicates significant difference between sexually naïve or experienced sex groups with the appropriate no sex control group (NS vs NNS, ES vs ENS; all p-values p<0.001; except H: ES vs ENS, p=0.008); # indicates significant difference between sexually naïve and experienced sex or no sex groups resp. (ES vs NS; p=0.049-<0.001; ENS vs NNS: p=0.028-<0.001).
Figure 5
Figure 5
Sexual behavior of GFP (n=12), ΔFosB (n=11) and ΔJunD (n=9) animals: mount latency (A), intromission latency (B), ejaculation latency (C), number of mounts (D), number of intromissions (E) and copulation efficiency (F). Data are expressed as group means (± SEM). * indicates significant difference from GFP (p=0.047-0.007); + indicates significant difference from ΔFosB (p=0.036-0.005); and # indicates a statistical difference between mating sessions 1 and 4 (GFP: p=0.025-<0.001; ΔFosB: p=0.036-<0.001).
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