What it takes to be at the top: The interrelationship between chronic social stress and social dominance

Abstract

Introduction: Dominance hierarchies of social animal groups are very sensitive to stress. Stress experienced prior to social interactions between conspecifics may be a determinant of their future social dynamics. Additionally, long-term occupancy of a specific hierarchical rank can have psychophysiological effects which increase vulnerability to future stressors.

Methods: We aimed to delineate differential effects of stress acting before or after hierarchy formation. We studied whether exposure to the chronic social defeat stress (CSDS) paradigm before a two-week-long hierarchy formation affected the attainment of a dominant status using the social confrontation tube test (TT). These animals were singly housed for at least one week before CSDS to decrease confounding effects of prior hierarchy experience. Additionally, we investigated whether social rank predicted vulnerability to CSDS, measured by a social interaction test.

Results: In TT, mice termed as dominant (high rank) win the majority of social confrontations, while the subordinates (low rank) lose more often. Within newly established hierarchies of stress-naïve mice, the subordinate, but not dominant, mice exhibited significantly greater avoidance of novel social targets. However, following exposure to CSDS, both lowest- and highest-ranked mice exhibited susceptibility to stress as measured by decreased interactions with a novel social target. In contrast, after CSDS, both stress-susceptible (socially avoidant) and stress-resilient (social) mice were able to attain dominant ranks in newly established hierarchies.

Conclusion: These results suggest that the response to CSDS did not determine social rank in new cohorts, but low-status mice in newly established groups exhibited lower sociability to novel social targets. Interestingly, exposure of a hierarchical social group to chronic social stress led to stress susceptibility in both high- and low-status mice as measured by social interaction.

Keywords: anxiety; chronic social stress; sociability; social dominance; social hierarchy.

FIGURE 1

Social confrontation tube test was validated to yield predominantly linear and stable hierarchies consistent with other measures of dominance. (a) Diagram of a confrontation trial. The subordinate mouse retreated from the tube first. (b) Representative image of the rank stability in a cage of four mice over the 4 days of testing. (c) Overall rank stability shows the average rank of animals belonging to each rank group (as determined at the end of TT) calculated for each day of testing for a total of N = 25 cages. (d) Winning ratio of ranked mice (N = 34–37 per rank) showed a significant linear trend from the most dominant to the most subordinate. (e) Individual daily trials and final hierarchies were predominantly linear. (f) The total time spent in the tube during a two‐day training phase did not differ between ranks (N = 20–25 per rank). (g) Weight was not a factor in establishing dominance as groups are weight‐matched prior to TT (N = 20–25 per rank). (h) Weights of ranked mice were comparable after testing (N = 20–25 per rank). (i) TT correlated with rankings from three other dominance tests: urine marking assay, UMA (p = .0509); agonistic behavior test, ABT (p = .0229); and the warm spot test, WST (p = .0090). Data are shown as mean ± SEM or box plot with whiskers denoting the min. and max. values. ****p < .0001

FIGURE 2

Chronic social defeat stress results in two distinct populations based on social interaction profiles that did not differ in subsequent hierarchy formation. (a) Timeline of behavioral studies investigating the effect of chronic stress on subsequent hierarchy formation. The age of mice is given in yellow boxes. (b) 15‐day CSDS paradigm consisted of daily sessions of 10 min physical stress followed by 24 hr of sensory stress. (c) Before chronic stress exposure, SI ratios did not differ between groups. (d) After CSDS, a subset of mice termed “stress‐susceptible” exhibited an SI ratio lower than that of “stress‐resilient” mice. (e) Levels of exploration, as measured by total distance travelled during the social session of the SI test, were comparable across stress groups. (f) Representative traces of the time spent interacting with a social target show that stress‐susceptible mice avoided the interaction zone around the social target mouse and escape to the corner zones. (g) None of the groups exhibited anhedonia following CSDS. (h) All groups exhibited similar daily wheel‐running activity profiles. (i) One CSDS‐exposed mouse was group‐housed with three stress‐naïve controls. (j) There was no difference in dominance between stress‐exposed groups. (k,l) Anxiety profiles in both OF and EPM anxiety tests did not differ between stress groups either before or after behavioral testing. N _{Stress‐naïve} = 57, N _Resilient = 10, N _Susceptible = 9 except for (g,h) where N _{Stress‐naïve} = 10, N _Resilient = 7, N _Susceptible = 6. Data are shown as mean ± SEM. **p < .01. ABT, agonistic behavior test; CSDS, chronic social defeat stress; EPM, elevated plus maze; OF, open field; SI, social interaction; SPT, sucrose preference test; TT, tube test; UMA, urine marking assay; WST, warm spot test

FIGURE 3

Baseline, but not post‐CSD, sociability is rank‐dependent. Change of social preference in rank 1 mice was significantly greater after CSD compared to rank 4 mice. (a) Timeline of behavioral studies investigating the effect of dominance status on susceptibility to chronic social stress. The age of mice is indicated in yellow boxes. (b) Pre‐CSDS: Following hierarchy formation, the winning and baseline SI ratios exhibited positive correlation, with dominant mice exhibiting higher sociability. (c) Post‐CSDS, winning and SI ratios of ranked mice did not differ significantly. (d) Rank 1 displayed a higher change in SI ratio following CSDS. (e) Rank 1 and rank 4 mice did not exhibit anhedonia in the SPT. (f) Daily wheel‐running activity profiles were similar across ranks. (g,h) There were no significant differences between groups in either trait or state anxiety tests. N _rank1 = 16, N _rank4 = 15, except for (e) where N _rank1 = 8, N _rank4 = 10 and (f) where N _rank1 = N _rank4 = 12. Data are shown as mean ± SEM. *p < .05. ABT, agonistic behavior test; CSDS, chronic social defeat stress; EPM, elevated plus maze; OF, open field; SI, social interaction; SPT, sucrose preference test; TT, tube test; UMA, urine marking assay; WST, warm spot test