Divergent changes in social stress-induced motivation in male and female mice

Exposure to stressors has been shown to dysregulate motivated behaviors in a bidirectional manner over time. The relationship between stress and motivation is relevant to psychological disorders, including depression, binge eating, and substance use disorder; however, this relationship is not well characterized, especially in females, despite their increased risk of these disorders. Social defeat stress is a common model to study stressinduced motivation changes, however, historically this model excluded females due to lack of female-tofemale aggression and unreliable male-to-female aggression. Additionally, changes in motivation are often assessed well after stress exposure ends, potentially missing or occluding changes to motivation during stress. Recently, the chronic non-discriminatory social defeat stress (CNSDS) model has demonstrated social defeat of male and female C57BL/6J mice by simultaneously exposing both mice to an aggressive male CD-1 mouse. Here we use this model to directly compare changes in the motivated behavior of male and female mice during and following chronic stress. We hypothesized that motivated behavioral responses would be dysregulated during stress and that the effects would worsen as the stress exposure continued. To monitor motivated behavior, mice had access to a Feeding Experimental Device.3 (FED3), a home cage device for operant responding. Operant responding was monitored prior to, during, and after stress by measuring nose pokes for sucrose pellets on a modified progressive ratio schedule of reinforcement. Our results demonstrated divergent behavioral outcomes between males and female mice in response to stress; where male mice increased motivated behavior during stress only, whereas female mice exhibited a decrease in motivation during and after stress. This study highlights the need to investigate the effects of stress-induced motivation over time, as well as the increased need to understand differences in the stress response in females.