Exploring the role of orexins in the modulation of social reward

Abstract

Abstract Rationale positive social interactions are essential for mental health, by offering emotional support, reducing stress levels, and promoting resilience against drugs of abuse effects. However, not all individuals perceive social interaction as rewarding. Objectives the goal of this study was to investigate whether the modulation of the orexin system can shift passive coping and non-social behavior (vulnerable) to active coping and social behavior (resilient). This knowledge is primordial for stress- and addiction-related disorders, and for other psychiatric disorders involving impairment in social interaction. Methods male C57/BL6N mice categorized into social and non-social groups, received injections of SB334867, a selective orexin 1 receptor (OX1R) antagonist, before the conditioning sessions with a male conspecific of the same weight and age. Results our results from the conditioned place preference test (CPP) show that SB334867 has no effect on social preference in non-social mice, but it reduces their stress levels and depression-like behavior. These effects appear to be due to a higher OX1R expression in the basolateral amygdala (BLA), a stress-related brain area, of non-social mice compared to their social counterparts. Conclusions these data suggest that the orexin system may be a target to alleviate stress and depression-like behavior in non-social individuals rather than to promote social reward.