Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Genes Brain Behav. 2013 Aug;12(6):666-72. doi: 10.1111/gbb.12060. Epub 2013 Jul 12.
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.
动机行为,包括性体验,激活中脑边缘多巴胺系统,并在伏隔核中产生持久的分子和结构变化。转录因子 ΔFosB 被假设部分介导这种经验依赖性可塑性。我们实验室的先前研究表明,在雌性叙利亚仓鼠的伏隔核中过度表达 ΔFosB 会增强性体验引起条件性位置偏好形成的能力。然而,尚不清楚 ΔFosB 介导的伏隔核转录是否是性奖励的行为后果所必需的。因此,我们使用腺相关病毒在伏隔核中过表达 ΔJunD,这是 ΔFosB 的显性负性结合伴侣,通过与 ΔFosB 竞争异二聚化,在结合靶基因启动子区域之前,降低 ΔFosB 介导的转录,从而阻止了重复性体验后的条件性位置偏好的形成。这些数据与我们之前的发现相结合,表明 ΔFosB 是性体验后行为可塑性所必需的。此外,这些结果有助于证明内源性 ΔFosB 表达在伏隔核中对自然奖励刺激的适应性反应的重要且不断增长的文献。