Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.
Nature. 2013 Sep 12;501(7466):179-84. doi: 10.1038/nature12518.
Social behaviours in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviours, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin acts as a social reinforcement signal within the nucleus accumbens core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the nucleus accumbens receives oxytocin-receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-hydroxytryptamine; 5-HT) innervation to the nucleus accumbens, abolishes the reinforcing properties of social interaction. Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-HT1B receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of oxytocin and 5-HT in the nucleus accumbens, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.
在蜜蜂和人类等各种物种中，社交行为促进了群体的生存，但往往会对个体造成一定的代价。尽管强化适应性社交互动显然是这些行为在进化上持续存在所必需的，但大脑如何编码社交奖励的神经机制在很大程度上仍是未知的。在这里，我们证明了在小鼠中，催产素在伏隔核核心中充当社交强化信号，在那里它引发兴奋性突触传递的突触前表达的长时程抑郁。尽管伏隔核从几个脑区接收含有催产素受体的输入，但这些受体（特别是来自中缝背核的受体）的基因缺失会消除社交互动的强化特性，中缝背核为伏隔核提供 5-羟色胺能（5-羟色胺；5-HT）支配。此外，催产素诱导的突触可塑性需要激活伏隔核 5-HT1B 受体，其阻断可防止社交奖励。这些结果表明，小鼠社交互动的奖励特性需要催产素和 5-HT 在伏隔核中的协调活动，这一机制上的见解对于理解自闭症等神经精神障碍中社交功能障碍的发病机制具有重要意义。
