Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation.

Ever since the discovery of the brain's orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin's source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell's role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin's impact on social interaction is multifactorial and depends on specific conditions available at a time.

Social Interaction Is Less Rewarding in Adult Female than in Male Mice.

(1) Background: Positive social relationships are essential for mental and physical health. However, not all individuals experience social interaction as a rewarding activity. (2) Methods: Social interaction reward in mice can be assessed by social conditioned place preference (CPP). The aim of this study is to investigate sex-dependent differences in the neurological underpinnings underlying social versus non-social phenotypes, using adult male and female C57BL/6J mice. (3) Results: Adult female mice expressed significantly less social reward than males from the same strain. Accordingly, pairs of male mice spent more time interacting as compared to female pairs. Subsequently, we analyzed neuropeptides previously reported to be important regulators of social behavior such as oxytocin, vasopressin, and orexin, in addition to Ca2+/calmodulin-dependent protein kinase II (αCaMKII), shown to be involved in social reward. Levels of neuropeptides and αCaMKII were comparable between males and females in all investigated regions. Yet, a significant negative correlation was found between endogenous oxytocin expression and social reward in female pairs. (4) Conclusions: Sex differences in the prevalence of many mental health disorders might at least in part be due to sex differences in social reward. Therefore, more research is needed to unravel the candidate(s) underlying this behavioral difference.