Accumulating evidence indicates that the central orexin (hypocretin) system plays an important role in regulating emotional processes in both humans and rodents. Thus, the orexin system has been repeatedly implicated in the pathophysiology of several neuropsychiatric disorders, such as anxiety disorders. Among others, symptoms like social fear and social withdrawal are frequently observed in these disorders. Based on this, we investigated the role of orexin deficiency in social (fear) behavior. For that, female and male orexin-deficient mice were tested for (1) sociability and social novelty, and (2) acquisition, expression, and extinction of conditioned social fear. We found that female orexin-deficient mice displayed reduced sociability and decreased preference for social novelty compared to their wild-type littermates. These effects of orexin deficiency were not observed in males. Moreover, orexin deficiency facilitated the acquisition and/or expression of conditioned social fear and impaired the extinction of social fear in both sexes. Taken together, our results indicate an important, partly sex-dependent, regulatory role of the orexin system in social (fear) behavior. Our findings support the hypothesis of orexin being an integrator of motivation, affect, and emotion.

越来越多的证据表明，中枢食欲素（hypocretin）系统在调节人类和啮齿动物的情绪过程中起着重要作用。因此，食欲素系统反复涉及几种神经精神疾病的病理生理学，例如焦虑症。其中，在这些疾病中经常观察到社交恐惧和社交退缩等症状。基于此，我们调查了食欲素缺乏在社交（恐惧）行为中的作用。为此，对雌性和雄性食欲缺乏的小鼠进行了 (1) 社交性和社交新奇性测试，以及 (2) 条件性社交恐惧的获得、表达和消失。我们发现，与野生型同窝小鼠相比，缺乏食欲素的雌性小鼠的社交能力降低，对社会新奇事物的偏好也降低。在男性中未观察到食欲素缺乏的这些影响。此外，食欲素缺乏促进了条件性社会恐惧的获得和/或表达，并损害了两性社会恐惧的消失。总之，我们的结果表明食欲素系统在社会（恐惧）行为中具有重要的、部分依赖于性别的调节作用。我们的发现支持了食欲素是动机、情感和情绪的整合者的假设。