Sexually divergent effects of social dominance on chronic stress outcomes in mice

Abstract

BackgroundSex and social context are two major factors in the development of depression and other stressrelated disorders. However, few studies of the effects of stress on rodent behavior and physiology have investigated social context and fewer still have assessed the possibility of sex-specific effects of social context. MethodsWe assessed social dominance of group-living mice during several days of monitoring using a high-throughput automated behavioral tracking system. We then exposed groups from each sex to a three-week chronic mild stress (CMS) procedure, followed by a behavioral test battery. Finally, we used principle component analysis and post-hoc tests to explore the sources of variance in the behavioral outcome data. ResultsWe found stable hierarchies in both sexes, however social dominance in males exhibited several additional associations with behaviors related to locomotion and exploration that were not seen in females. Crucially, pre-stress social dominance status was associated with opposing outcomes on multiple behavioral readouts between the two sexes following CMS. In particular, subordinate male mice and dominant female mice appeared more responsive to the environmental challenge, as observed in anxiety-like and locomotor behaviors. ConclusionsThis work demonstrates that sex differences interact with preexisting social dominance status to alter the effects of chronic stress. It highlights the importance of understanding the interplay between sex and social context and its contribution to individual differences in stress response.

Individual differences in social homeostasis

“…In the previous sections, we argued that sex differences might impact an individual's set point as well as behavioral effector mechanisms, particularly in the context of stress. The two main factors in the development of stress-related disorders, like depression, are sex and social context (Karamihalev et al, 2020).…”

Distinct prefrontal projections conversely orchestrate social competition and hierarchy

“…Many social animals compete for limited resources such as food and territory, resulting in a social hierarchy within a group. An individual's social rank determines the behaviors that are appropriate for that position 1,2,3,4,5,6,7,8 . For instance, social subordinates avoid competing with social dominants to prevent physical harm and energy loss, whereas social dominants engage in agonistic interactions to obtain easy access to food and sexual partners.…”