Post stress sensory contact with a male mouse is associated with altered social behavior in a female vicarious social defeat stress model

Depression affects females more than males, with responses to antidepressants also exhibiting a distinct difference between sexes. Stress models in rodents have predominantly been developed for males, and their application in females remains challenging. This study investigated how post stress sensory contact with male mice affects the behavioral outcomes of female C57BL/6JJcl (B6) mice subjected to vicarious social defeat stress (VDS). We compared three types of VDS paradigms in female mice: the conventional paradigm and two adapted protocols that eliminated sensory contact with male ICR mice during the post-stress period under either single-housed (SH) or pair-housed (PH) conditions. In the conventional paradigm, female B6 mice did not exhibit a significant increase in social avoidance. In contrast, in the adapted paradigm, social avoidance behavior was observed in the PH group, indicating that post stress sensory contact with male ICR affects the stress susceptibility of female VDS model. Furthermore, the estrous cycle stage did not affect social avoidance behavior in each group. Next, we compared two different housing conditions to examine the appropriate method for eliminating sensory contact in female VDS model. SH mice showed reduced feed intake, increased water consumption, and attenuated body weight gain, regardless of VDS exposure. These findings suggest that post-stress sensory contact with a male mouse may influence social behavior in female mice exposed to VDS. The present study highlights the potential impacts of these experimental variables when interpreting behavioral outcomes in female VDS models.