Sex Differences in Reaction to Chronic Unpredictable Stress in the House Mouse (Mus m. musculus) of Wild Origin

Sex differences in stress response continue to be understudied in basic physiological and behavioral research. Current study aimed to investigate the sex-specific effects of chronic stress in wild-derived house mice subjected to chronic unpredictable stress (CUS). The use of mice from the wild enhanced ecological validity of our stress model. We applied CUS for 5 weeks based on protocols previously established in laboratory mice. Control mice were not subjected to stress. After the 5-week experiment, behavioral tests were performed, blood and hair samples were collected for corticosterone measurement, stress-sensitive organ weights were assessed. Stressed females, but not stressed males, gained significantly less body weight over the entire CUS period. After CUS, mice tended to have higher adrenal and thymus weights. In stressed females, we observed significantly prolonged grooming time in open field test and fewer immobility episodes in tail suspension test (TST). Stressed males displayed significantly shorter immobility time in TST. Stressed males, but not stressed females, had significantly higher levels of hair corticosterone, with a similar tendency in plasma. Our results indicate different CUS coping strategies in males and females and raise a question about development of different protocols for assessment stress response in males and females.