Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions.

中文翻译：

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VTA中的地西p作用通过激活多巴胺D1受体来增强伏隔核中的社会优势和线粒体功能。

苯二氮卓类药物可以缓解社会骚扰并增加社会竞争，特别是在高焦虑人群中。但是，尚不了解苯二氮卓类药物在社会竞争中发挥作用的神经回路和机制。越来越多的证据表明，中脑边缘系统是至少某些苯二氮杂pine介导的作用的潜在作用部位。此外，伏隔核（NAc）中的线粒体功能与焦虑和社会竞争力之间的联系有因果关系。在这里，我们显示地西epa促进了社会主导地位，减轻了高焦虑大鼠表现出的竞争劣势和低NAc线粒体功能，并将腹侧被盖区（VTA）确定为直接地西epa作用的关键作用部位。我们还显示，VTA地西epa内输注可增加伏安性多巴胺和DOPAC，以及多巴胺D1但不包含D2的细胞的活性。此外，NAc内输注D1（而非D2）受体激动剂有助于社会优势和线粒体呼吸。相反，VTA内地西epa对社会优势和NAc线粒体呼吸的作用被线粒体复合物I抑制剂或D1受体拮抗剂的药理学NAc微输注所阻断。我们的数据支持以下观点：地西epa会抑制VTA多巴胺能神经元，从而导致多巴胺释放到NAc中，其中D1信号的激活会暂时促进线粒体功能，即增加呼吸作用并增强ATP水平，从而最终增强社会竞争行为。所以，