Department of Psychology, University of California, Davis, CA 95616, USA.
Neuroscience. 2012 May 17;210:266-74. doi: 10.1016/j.neuroscience.2012.03.019. Epub 2012 Mar 17.
The nucleus accumbens is a key region that mediates aspects of immediate and long-term adaptations to various stimuli. For example, both repeated amphetamine and pair-bonding increase dopamine D1 receptor binding in the nucleus accumbens of the monogamous prairie vole (Microtus ochrogaster). This upregulation has significant and stimulus-dependent behavioral consequences. A promising candidate for these and other adaptations is the transcription factor ΔfosB. ΔfosB is a highly stable protein that persists in the brain over long periods of time, leading to increasing and accumulating levels with repeated or continuous exposure to specific stimuli. Within the nucleus accumbens, ΔfosB is specifically increased in medium spiny neurons containing D1 receptors. To explore whether ΔfosB is altered by drug and social experience in prairie voles, we performed three separate experiments. In the first experiment, animals were treated with repeated injections of amphetamine and then brain tissue was analyzed for ΔfosB expression. As expected, 4 days of amphetamine treatment increased ΔfosB in the nucleus accumbens, consistent with previous findings in other laboratory species. In the second experiment, animals were housed for 10 days with one of three social partners: a familiar same-sex sibling, an unfamiliar same-sex partner, or an unfamiliar opposite-sex partner. Here, we predicted that 10 days of housing with an opposite-sex partner would act as a "social reward," leading to upregulation of ΔfosB expression in the nucleus accumbens. In a third experiment, we also investigated whether 10 days of social isolation would result in altered ΔfosB activity. We hypothesized that isolation would lead to decreased levels of nucleus accumbens ΔfosB, as seen in other studies. However, neither opposite-sex cohabitation nor social isolation affected ΔfosB expression in the nucleus accumbens. These findings suggest that social stimuli, in contrast to drugs of abuse, are not mediators of ΔfosB in this region in prairie voles.
伏隔核是介导各种刺激的即时和长期适应的关键区域。例如,重复使用安非他命和配对结合都会增加一夫一妻制草原田鼠(Microtus ochrogaster)伏隔核中的多巴胺 D1 受体结合。这种上调具有显著的刺激依赖性行为后果。这种适应和其他适应的一个有希望的候选者是转录因子 ΔfosB。ΔfosB 是一种高度稳定的蛋白质,在大脑中长时间存在,导致随着对特定刺激的重复或连续暴露,水平不断增加和积累。在伏隔核中,ΔfosB 特异性地增加了含有 D1 受体的中型多棘神经元。为了探讨 ΔfosB 是否因草原田鼠的药物和社会经验而改变,我们进行了三项独立的实验。在第一个实验中,动物接受了重复的安非他命注射,然后分析脑组织中的 ΔfosB 表达。正如预期的那样,4 天的安非他命处理增加了伏隔核中的 ΔfosB,与其他实验室物种的先前发现一致。在第二个实验中,动物与三个社会伴侣中的一个共同生活了 10 天:一个熟悉的同性兄弟姐妹、一个陌生的同性伴侣或一个陌生的异性伴侣。在这里,我们预测与异性伴侣共同生活 10 天会作为一种“社会奖励”,导致伏隔核中 ΔfosB 表达的上调。在第三个实验中,我们还研究了 10 天的社会隔离是否会导致 ΔfosB 活性改变。我们假设隔离会导致伏隔核中 ΔfosB 水平降低,正如其他研究中所见。然而,异性同居或社会隔离都不会影响伏隔核中 ΔfosB 的表达。这些发现表明,与滥用药物相比,社会刺激不是草原田鼠该区域中 ΔfosB 的介导物。