Male and Female Mice Are Similarly Susceptible to Chronic Nondiscriminatory Social Defeat Stress Despite Differences in Attack Frequency from Aggressor.

Rationale: Mood disorders are often precipitated by chronic stress and can result in an inability to adapt to the environment and increased vulnerability to challenging experiences. While diagnoses of mood disorders are diagnosed twice as frequently in women than in men, most preclinical chronic social defeat stress mouse models exclude females due to decreased aggression toward female intruders. Objectives: We previously reported that the chronic non-discriminatory social defeat stress (CNSDS) paradigm is effective in both sexes, allowing for comparisons between male and female mice. We aimed to improve the screening protocol to identify CD-1 aggressors for use in CNSDS and the method for determining susceptibility to CNSDS. Finally, we aimed to determine whether susceptibility to CNSDS correlated with impaired performance in a satiety-based outcome devaluation task. Methods: We analyzed CNSDS screening and social defeat sessions to determine appropriate parameters for selecting CD-1 aggressors and investigated aggressions toward male and female intruder mice. We also investigated CNSDS effects on a reward valuation task. Results: We observed that despite receiving fewer attacks, female mice are equally susceptible to CNSDS as males and that CNSDS abolished satiety-based outcome devaluation in susceptible male and female mice, but not in resilient male and female mice. Conclusions: These data suggest that CNSDS-defined susceptible and resilient phenotypes extend to reward behaviors.