Orexin deficiency affects sociability and the acquisition, expression, and extinction of conditioned social fear.

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.