Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype

Abstract

AbstractStress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are nega9vely affected in the future. Stress responses are established by an interplay between gene9cs, environment, and life experiences. Psychosocial stress is par9cularly impacAul during adolescence, a cri9cal period for the development of mood disorders. In this study we compared two established, selec9vely-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to inves9gate how gene9c temperament and adolescent environment impact future responses to social interac9ons and psychosocial stress, and how these determinants of stress response interact. Animals were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interac9on and anxiety-like behavior. Adolescent enrichment caused bLR rats to display less social avoidance, more social interac9on, less submission during defeat, and resilience to the prolonged effects of social stress on cor9costerone, while enrichment caused bHR animals to show greater aggression during defeat and during a neutral social encounter, and decreased anxiety-like behavior. To gain insight into the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regula9on and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory ac9vity were enriched with differen9al expression in both regions, with a par9cularly large effect on gene sets that regulate social behaviors. These findings provide further evidence that adolescent enrichment can serve as an inocula9ng experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipula9ng their environment has transla9onal implica9ons, as it underscores the feasibility of interven9on strategies targeted at gene9cally vulnerable adolescent popula9ons.