A Novel Method for Chronic Social Defeat Stress in Female Mice

Historically, preclinical stress studies have often omitted female subjects, despite evidence that women have higher rates of anxiety and depression. In rodents, many stress susceptibility and resilience studies have focused on males as one commonly used paradigm-chronic social defeat stress-has proven challenging to implement in females. We report a new version of the social defeat paradigm that works in female mice. By applying male odorants to females to increase resident male aggressive behavior, we find that female mice undergo repeated social defeat stress and develop social avoidance, decreased sucrose preference, and decreased time in the open arms of the elevated plus maze relative to control mice. Moreover, a subset of the female mice in this paradigm display resilience, maintaining control levels of social exploration and sucrose preference. This method produces comparable results to those obtained in male mice and will greatly facilitate studying female stress susceptibility.