Social instability in female rodents as a model of stress related disorders: A systematic review

The risk of developing stress related disorders such as depression is two times higher in women than in men, and social stress is considered the principal etiology for this disorder. Social defeat animal model is the most common procedure to induce social stress in male rodents, but the stressful stimulus and the stress response can be different for each sex. In this regard, social defeat stress model does not fit the social nature of females, and according to the emerging evidence, the social instability stress (SIS) model could be a suitable procedure to investigate this stress related disorder in females. This study aims to systematically review the effects of SIS on physiological and behavioral parameters involved in the pathophysiology of depression, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method on PubMed, Medline and Web of Science. Seventeen studies met the inclusion criteria. The reported physiological measures comprised the hypothalamic-pituitary-adrenal axis activity, neurotrophic factors, immune and monoaminergic systems, vasopressin and oxytocin receptors, sex hormone levels and estrus cycle, while main behavioral measures involved sucrose preference test, forced swimming test, elevated plus maze, open field test and social interaction. This systematic review revealed a wide variability on the social instability regimen and on the measured variables. However, all studies agree that SIS model can elicit behavioral and physiological alteration involved in stress related disorders, with HPA axis hyperactivity, increased anxiety-like behavior and disrupted reward system being the most repeated outcomes. A unified SIS application criterion is required in order to obtain consistent data and elucidate the underlying mechanisms of anxiety and depression in females.