Voluntary wheel running ameliorates abnormalities in social behavior induced by social isolation: Involvement of neural and neurochemical responses.

Social isolation (SI) can lead to devastating behavioral effects. Increasing evidence has demonstrated that physical activity can improve sociability and brain functions, but whether voluntary exercise can ameliorate SI-induced abnormalities in social behavior and its underlying neuronal mechanisms remains unknown. The present study found that SI during adulthood increased aggression in the resident-intruder test and motivation for social exploration in the three-chamber test. Voluntary wheel running (VWR) could reverse the alterations in social behavior induced by SI in male mice. In addition, SI increased the number of c-Fos-immunoreactive neurons and c-Fos/AVP-labeled neurons in the PVN, reduced c-Fos/TPH2-labeled neurons in the DRN. These alterations could be reversed by VWR. Together, our results reveal that voluntary exercise could ameliorate SI-induced negative effects on social behavior, possibly via alterations of neuronal activation in the brain. This finding provides a potential therapy and targets to prevent or treat the psychological diseases associated with abnormalities in social behaviors.