Despite females accounting for the majority of individuals suffering from psychiatric disorders, preclinical studies have almost exclusively focused on male subjects, partly due to the lack of ideal female animal paradigms. Developing effective models for studying psychiatric disorders in female animals remains a long-standing scientific challenge in the life sciences. A "Multiple Integrated Social Stress (MISS) model" in C57BL/6J female mice was recently established by simulating and integrating social risk factors that contribute to the development of psychiatric disorders. To establish this MISS paradigm, female C57BL/6J mice were randomly subjected each day, for ten consecutive days, to a sequence of stressors: social competition failure in the tube test, modified vicarious social defeat stress, inescapable overcrowding stress, and subsequent social isolation. Compared to naïve mice, MISS-exposed mice exhibited depressive- and anxious-like phenotypes, as measured by the sucrose preference, tail suspension, open field, and elevated plus maze tests. This paradigm offers a valuable tool for investigating the neurobiological mechanisms underlying depression and anxiety in females, particularly those with ambiguous etiology and complex symptomatology.
Zhai et al. (2025) studied this question.