Female rats are more responsive than are males to the protective effects of voluntary physical activity against the behavioral consequences of inescapable stress

Abstract Common stress-related mental health disorders affect women more than men. Physical activity can provide protection against the development of future stress-related mental health disorders (i.e. stress resistance) in both sexes, but whether there are sex differences in exercise-induced stress resistance is unknown. We have previously observed that voluntary wheel running (VWR) protects both female and male rats against the anxiety- and exaggerated fear-like behavioral effects of inescapable stress, but the time-course and magnitude of VWR-induced stress resilience has not been compared between sexes. The goal of the current study was to determine whether there are sex differences in the time-course and magnitude of exercise-induced stress resistance. In adult female and male Sprague Dawley rats, 6 weeks of VWR produced robust protection against stress-induced social avoidance and exaggerated fear. The magnitude of stress protection was similar between the sexes and was independent of reactivity to shock, general locomotor activity, and circulating corticosterone. Interestingly, 3 weeks of VWR prevented both stress-induced social avoidance and exaggerated fear in females but only prevented stress-induced social avoidance in males. Ovariectomy altered wheel-running behavior in females such that it resembled that of males, however; 3 weeks of VWR still protected females against behavioral consequences of stress regardless of the absence of ovaries. These data indicate that female Sprague Dawley rats are more responsive to exercise-induced stress resistance than are males. GRAPHICAL ABSTRACT HIGHLIGHTS The duration of wheel running required to enable stress resistance differs between the sexes in a behavior-dependent manner. Wheel running enables rapid protection against stress-induced social avoidance in both male and female Sprague Dawley rats. Wheel running enables protection against stress-induced exaggerated fear more readily in female Sprague Dawley rats compared to males. Ovarian hormones are not necessary for stress-protection produced by 3 weeks of wheel running in female Sprague Dawley rats.