Susceptibility and resilience to chronic social defeat stress in adolescent male mice: No correlation between social avoidance and sucrose preference

Abstract

Psychosocial stress is the major form of stress faced by children and adolescents and is an important risk factor for the development of mental illnesses. Chronic social defeat stress (CSDS) is a preclinical mouse model that induces an entire spectrum of phenotypes with similar interindividual variability as seen in humans. Following CSDS, adult male mice have been characterized as being either susceptible or resilient to emotional stress on the basis of their social interactions, which was reported to be highly correlated with sucrose preference (SP) when measured after the last defeat episode.We studied adolescent male C57BL/6 mice (30 days old) for susceptibility and resilience to social avoidance, anhedonia and anxiety-like behaviors, body weight change and basal blood corticosterone concentrations after 10 days of CSDS. Defeated adolescents showed reduced SP, reduced social interaction time (with an unknown adolescent male from their same strain), reduced weight gain and higher basal blood corticosterone concentration when compared to nondefeated mice. Only a small proportion of defeated adolescents were either totally susceptible (20%) or totally resilient (30%) in both the SP and social avoidance tests. The remaining defeated mice had a distinct behavioral impairment - susceptible in one test and resilient in the other. Surprisingly, behaviorally resilient defeated adolescents were the most affected population in terms of both endocrine/physiological outcomes. These findings illustrate that, contrary to prior assumptions in adults, the CSDS responses are more complex and singular in adolescents, and caution should be taken for the correct interpretation of those phenotypes. We propose a better characterization of social defeat stress responses as a critical step to advance our understanding of the mechanisms behind stress resilience that translate to human experience.