Social status mediates isolation stress response and mood related symptoms in female mice
Social isolation (SI) is recognized as a major risk factor for physical and psychological health problems in humans and other social species. Across species, long-term SI has been shown to increase anxiety and depressive symptoms, weaken immunity, and reduce central glucocorticoid receptor sensitivity to inhibition, leading to heightened stress responses. In our study, we investigated the effect of SI on female mice since stress-related disorders such as major depression and generalized anxiety disproportionately affect women. Importantly, we want to explore how social status moderates the effect of SI stress on the manifestation of anxiety and depressive phenotypes. This study may provide valuable neurobiological insights into what makes an individual vulnerable to isolation stress, an especially timely topic given the lockdown restrictions due to the COVID-19 pandemic. In these experiments, we holistically study SI by incorporating data from behavioral paradigms, fecal corticosterone measurements, and histological assessment of c-Fos, an indirect marker of brain activity. We found that chronic SI did not induce anxiety-related behavior, but it did increase stress response and induce depression-like behavior in the experimental group. Moreover, in the experimental group, subordinate animals were especially sensitive to SI and had significant deterioration in coat state compared to dominant mice.