ΔJunD overexpression in the nucleus accumbens prevents sexual reward in female Syrian hamsters

Abstract

Motivated behaviors, including sexual experience, activate the mesolimbic dopamine system and produce long-lasting molecular and structural changes in the nucleus accumbens. The transcription factor ΔFosB is hypothesized to partly mediate this experience-dependent plasticity. Previous research in our laboratory has demonstrated that overexpressing ΔFosB in the nucleus accumbens of female Syrian hamsters augments the ability of sexual experience to cause the formation of a conditioned place preference. It is unknown, however, whether ΔFosB-mediated transcription in the nucleus accumbens is required for the behavioral consequences of sexual reward. We therefore used an adeno-associated virus to overexpress ΔJunD, a dominant negative binding partner of ΔFosB that decreases ΔFosB-mediated transcription by competitively heterodimerizing with ΔFosB before binding at promotor regions on target genes, in the nucleus accumbens. We found that overexpression of ΔJunD prevented the formation of a conditioned place preference following repeated sexual experiences. These data, when coupled with our previous findings, suggest that ΔFosB is both necessary and sufficient for behavioral plasticity following sexual experience. Furthermore, these results contribute to an important and growing body of literature demonstrating the necessity of endogenous ΔFosB expression in the nucleus accumbens for adaptive responding to naturally rewarding stimuli.

Keywords: Adeno-associated virus; conditioned place preference; delta FosB; plasticity; sex.

Figure 1. AAV injections

A) AAV injections for the four experimental groups were localized to the dorsal nucleus accumbens core. Circles represent animals injected with AAV-GFP-ΔJunD, whereas squares represent animals injected with AAV-GFP. Filled symbols represent animals that received sexual experience, whereas open symbols represent animals that remained sexually-naïve. Numbers represent distance relative to bregma, ac, anterior commissure. B) Photomicrograph of representative nuclear immunostaining for JunD protein, scale bar = 200 μm. C) Photomicrograph of representative immunostaining for GFP in cell bodies and processes.

Figure 2. Overexpression of ΔJunD in the NAc does not affect the expression of female sexual behavior

During sexual experience trials, females injected with AAV-GFP-ΔJunD did not differ from females injected with AAV-GFP in A) the latency to express lordosis or B) the total duration of lordosis on any test day. Data expressed as means ± standard errors.

Figure 3. Overexpression of ΔJunD in the NAc prevents the formation of conditioned place preference following sexual experience

During the post-test, females who were injected with AAV-GFP and received sexual experience spent significantly more time in their initially non-preferred chamber (i.e., the chamber in which they received sexual experience) than they did during the pre-test. In contrast, the amount of time spent in the non-preferred chamber did not differ between the pre- and post-test for females injected with AAV-GFP-ΔJunD that received sexual experience. Likewise, females who were injected with either AAV-GFP or AAV-GFP-ΔJunD and did not receive sexual experience did not differ in the amount of time they spent in the non-preferred chamber during the pre- and post-tests. Data expressed as means ± standard errors. *significant difference between pre- and post-test (p < 0.05)