The Effect of Adolescent Environmental Enrichment and Social Defeat on the Nucleus Accumbens and Hippocampus in a Selectively Bred Model with Anxious Phenotype (bLR Rats): RNAseq data
Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions 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 interaction and anxiety-like behavior. Adolescent enrichment caused bLR rats to display less social avoidance, more social interaction, less submission during defeat, and resilience to the prolonged effects of social stress on corticosterone, 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 regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. These findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations. Overall design: The RNA-sequencing component of this study examined gene expression in the nucleus accumbens (NACC) and hippocampus (HC) in male bLR rats that had either experienced social and environmental enrichment (EE) or standard housing (NIL) during adolescence (P35-P60), and then received either four days of social defeat (SD: P61-64) or a no defeat control condition (NIL). All animals then received behavioural testing (P65-67) to measure social interaction and anxiety-like behavior (elevated plus maze). On P68, the animals were sacrificed. Brain tissue from the nucleus accumbens and hippocampus was collected for RNA-Sequencing, and blood was collected for plasma hormone measurements (corticosterone, testosterone). When reusing this data, please note that many of the batch-related or technical variables (generation, dissection date, RNA extraction date, RNA concentration) were found to influence behavioral, hormonal, or gene expression findings and should be included as co-variates in models when applicable.