CHARACTERIZING BEHAVIORAL CHANGES FOLLOWING ACUTE AND CHRONIC SOCIAL DEFEAT STRESS IN MALE AND FEMALE MICE: SEX-SPECIFIC MANIFESTATIONS OF RESILIENCE AND SUSCEPTIBILITY

Stressful events are a major risk factor for the development of psychiatric disorders such as anxiety and depression. Despite decades of treatment focused research efforts, these disorders continue to impose substantial individual and societal burdens. Individual responses to stress are highly heterogeneous with some individuals developing long-lasting behavioral and emotional disturbances, while others remain stable or resilient. This variability is well captured in rodent models. Following social defeat, mice can be reliably stratified into resilient or susceptible subgroups based on performance in a post-stress social interaction (SI) test. In addition, sex-differences in stress responses are well documented but remain relatively underexplored. We are interested in identifying distinct predictors of susceptibility and resilience in males and females. To address this, we used an extensive behavioral battery to characterize behavioral changes following acute social defeat stress and correlated these with performance in the same tests following chronic social defeat stress. Mice were classified as resilient or susceptible based on SI scores following stress. We observed sex differences in the proportion of resilient animals. Furthermore, we identified sex-specific behavioral profiles in the elevated plus maze, three-chamber social interaction test, and light/dark box. These findings suggest that vulnerability to stress may manifest differently in males and females and may not be fully captured by classic measures of susceptibility. Ongoing analyses aims to further define sex-dependent behavioral patterns and relationships between acute and chronic stress responses. Together, this work may provide insight into distinct vulnerability profiles and inform the development of preventative strategies.