Sex differences in the chronic mild stress model of depression

Abstract

A large volume of clinical and experimental evidence documents sex differences in brain anatomy, chemistry, and function, as well as in stress and drug responses. The chronic mild stress model (CMS) is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents despite the markedly higher prevalence of major depression among women. Herein, we review CMS studies conducted in rats and mice of both sexes and further discuss intriguing sex-dependent behavioral and neurobiological findings. The PubMed literature search engine was used to find and collect all relevant articles analyzed in this review. Specifically, a multitermed search was performed with 'chronic mild stress', 'chronic unpredictable stress' and 'chronic variable stress' as base terms and 'sex', 'gender', 'females' and 'depression' as secondary terms in various combinations. Male and female rodents appear to be differentially affected by CMS application, depending on the behavioral, physiological, and neurobiological indices that are being measured. Importantly, the CMS paradigm, despite its limitations, has been successfully used to assess a constellation of interdisciplinary research questions in the sex differences field and has served as a 'silver bullet' in assessing the role of sex in the neurobiology of major depression.

Differential effects of photoperiod length on depression- and anxiety-like behavior in female and male diurnal spiny mice

“…A C C E P T E D M A N U S C R I P T previously reported in animal studies, and they concur with the difference in prevalence of affective disorders in men and women [25,44].…”

Treatment-resistant depression: are animal models of depression fit for purpose?

“…However, in the learned helplessness and CMS models, female rats are actually less likely than males to develop depressive behaviours (Dalla et al 2010;Franceschelli et al 2014). Therefore, female sex is not associated with increased stress responsiveness in either people or rodents.…”

Predictive behaviors for anxiety and depression in female Wistar rats subjected to cafeteria diet and stress

“…In addition, some studies have pointed to different results when males and females are evaluated in studies involving obesity [2] and stress [4,32,42,52]. Especially on stress, various stressor agents and protocols have been used.…”

“…Especially on stress, various stressor agents and protocols have been used. According to Franceschelli et al [32], the chronic mild stress model is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents.…”