Voluntary exercise mitigates the effects of peri‐adolescent social isolation on emotion recognition and the oxytocinergic system in male mice

Social isolation, particularly during adolescence, is known to affect cognitive, emotional, and social behaviors as well as brain modulatory systems such as the hypothalamic oxytocinergic system. Interestingly, recent evidence indicates that exercise can exert beneficial effects on behaviors through the activation of the oxytocinergic system. Weaned male mice were either singly- or group-housed and were exposed to either an igloo or a running wheel until the end of the experiment. After 12 weeks in these experimental conditions, they were subjected to various behavioral tests to assess different dimensions of social behaviors (sociability, social recognition and emotion discrimination), anxiety levels, and spatial memory. The impact of peri-adolescent social isolation and of voluntary running activity on the oxytocinergic system was also evaluated. We found that peri-adolescent social isolation enhanced social investigation (social rebound) and impaired emotion discrimination in male mice, without affecting social novelty recognition, spatial memory or anxiety-like behavior. Social isolation also decreased the number of oxytocinergic neurons in the hypothalamic paraventricular nucleus, but not in the supraoptic nucleus, and did not affect circulating OXT levels. Voluntary exercise protected against social isolation-induced deficits in affective state discrimination and enhanced OXT plasma levels without altering the number of oxytocinergic neurons. Our results indicate that peri-adolescent isolation particularly alters socio-affective discrimination and the oxytocinergic system, that are mitigated by voluntary exercise. This suggests that exercise could alleviate emotion discrimination deficits induced by isolation, possibly through the improvement of oxytocinergic signaling.