TY - JOUR T1 - Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice JF - bioRxiv DO - 10.1101/550525 SP - 550525 AU - Christine N. Yohn AU - Sandra A. Ashamalla AU - Leshya Bokka AU - Mark M. Gergues AU - Alexander Garino AU - Benjamin A. Samuels Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/02/14/550525.abstract N2 - Despite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice. ER -