Adolescent environmental enrichment prior to social stress induces resilience in a novel rodent model of vulnerability
O'Connor AM, Hebda-Bauer EK, Watson SJ, Akil H
Society for Neuroscience. 2019.
Selectively bred High Responder (bHR) and Low Responder (bLR) rats are a novel rodent model of mood disorders. bHRs emulate externalizing mood disorders and are resilient to stressors, while bLRs emulate internalizing mood disorders and are vulnerable to stressors. Adult environmental enrichment (EE) decreases anxiety-like behavior of bLRs and alters social behavior of bHRs. Adolescence is a critical period for emotional circuitry and a time of increased vulnerability to environmental influences and stressors. bHR and bLR rats show differing phenotypes by adolescence, suggesting that they may respond differently to EE and stressors during this time. This study examines the impact of adolescent EE on anxiety-like behavior of bHR and bLR animals experiencing a social stressor. Male animals from generations F49, F53 and F56 of the bHR/bLR colony were placed in EE for 1 hour/day/5 days a week starting at 35 days postnatal (P35) and ending at P60. Control animals were standard housed with no handling. Half of all animals underwent social defeat (SD) from P61-P64. All animals underwent behavioral testing consisting of open field on P65, social interaction on P66 and elevated plus maze (EPM) on P67. All animals were sacrificed on P68 and brains and plasma collected. Plasma hormone levels were assessed using ELISA kits for testosterone and corticosterone. Social defeat increased bLR freezing, and bHR exploration, within the open field; EE increased exploratory behavior on the EPM in bHRs but not bLRs. Adolescent EE prior to SD decreased social anxiety in bLRs, with EE + SD animals showing decreased social avoidance, increased social interaction and altered ultrasonic vocalizations (USV) compared to standard housed bLR rats experiencing SD. Social interaction behavior was similarly changed in bHRs, without the concomitant changes in USVs. Thus, bLR EE + SD animals behaved similarly to bHR EE + SD animals during social interaction testing, and were more sociable than baseline bHRs. Adolescent EE decreased bLR plasma testosterone and there was no impact of either EE or SD on plasma corticosterone levels. This data shows that bLR animals that experienced EE prior to SD showed bHR-like patterns of social interaction behavior, with greater changes in USV production and social engagement than bHRs. Adolescent EE flips the bLR social behavior phenotype after social stress, providing evidence that genotype-environment interactions can induce resilience in a usually vulnerable line. This behavioral change does not appear to be mediated by circulating testosterone or corticosterone; work is underway to determine the neural underpinnings of this adolescent reprogramming.