Early-life stress alters adult social and coping behaviors in a sex-specific and domain-dependent manner

Early Life Stress (ELS) increases the risk for mental health issues in humans, notably in major depression and anxiety disorders. ELS is frequently modeled in laboratory rodents by disrupting the early postnatal environment. Literature on ELS is expanding, yet studies on sex-specific differences remain mixed. We utilized a novel ELS protocol that subjected mouse pups of both sexes to maternal separation and removed pup-to-pup contact comfort during postnatal days 10 to 17. We hypothesized that this ELS protocol would induce depressive and anxiety-like phenotypes persisting into adulthood, with greater vulnerability in females. A second cohort reared under normal conditions until adulthood was subjected to forced swim, mimicking adult-onset stress (AS). ELS, AS, and control animals (reared under normal conditions) underwent open field, social interaction, and tail suspension tests. In open field, AS mice spent significantly less time in center than controls. Social interaction showed significant effects of treatment and sex, with stress exposure increasing familiar-mouse interaction time and reducing the sex difference observed in controls. Tail suspension testing revealed a significant decrease in latency to immobility for stress groups compared to controls. Total time immobile showed significant group and interaction effects, with stress groups showing more time immobile. Both social interaction and tail suspension revealed a sex difference in controls, eliminated in stress groups. This ELS protocol produces lasting alterations in adult social and coping-related behaviors and demonstrates multiple sex-specific outcomes.