PT  - JOURNAL ARTICLE
AU  - Stoyo Karamihalev
AU  - Elena Brivio
AU  - Cornelia Flachskamm
AU  - Rainer Stoffel
AU  - Mathias V. Schmidt
AU  - Alon Chen
TI  - Sexually divergent effects of social dominance on chronic stress outcomes in mice
AID  - 10.1101/2020.02.04.933481
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.04.933481
4099  - http://biorxiv.org/content/early/2020/02/04/2020.02.04.933481.short
4100  - http://biorxiv.org/content/early/2020/02/04/2020.02.04.933481.full
AB  - Background Sex and social context are two major factors in the development of depression and other stress-related 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.Methods We 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.Results We 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.Conclusions This 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.CMSchronic mild stress;SBSocial Box;DSDavid’s Score;OFTopen field test;EPMelevated plus maze;PCAprinciple components analysis.