A novel chronic social stress paradigm in female mice

Major depression is one of the most prevalent stress-related psychiatric diseases. Next to environmental influences such as chronic social stress, gender is among the strongest risk factors for major depression, with women having a twice as high risk to develop the disease compared to men. While there is abundant literature on the effects of chronic social stress in male rodents, there is a serious lack of information on gender-specific effects. Especially in mice, which due to the wide availability of transgenic lines offer a unique opportunity to study gene x environment interactions, there is no existing model of chronic social stress that is applicable to both sexes. We here describe the effects of chronic social stress based on the disruption of the social network in a group-housed situation in female mice, a model that was recently described and validated for male mice. In this model, the group composition of the mice is changed twice per week for a period of 7 weeks, covering the adolescent and early adulthood period. We observed that housing in an unpredictable social environment resulted in chronic stress in female mice. The observed effects, which included increased adrenal weight, decreased thymus weight, increased corticosterone levels, and increased anxiety-like behavior, were very similar to the described effects of this paradigm in male mice. In addition, we observed a distinct expression of stress system-related genes in female mice following chronic stress exposure. Our results validate this model as a suitable approach to study chronic social stress in female mice and open up the opportunity to use this model with transgenic or knockout mouse lines.