Acute stress imposed during adolescence has minimal effects on hypothalamic-pituitary-adrenal (HPA) axis sensitivity in adulthood in female Sprague Dawley rats

Abstract

Adolescence is a developmental epoch marked by maturation of stress-responsive systems including the Hypothalamic-Pituitary-Adrenal (HPA) axis. Emerging evidence has found sex-specificity in the long term behavioral and neural effects of stressors experienced during this sensitive period, though most studies have utilized chronic stress exposures that span much of the adolescent period. Using Sprague-Dawley rats, we examined how a single exposure to inescapable footshock (80 shocks, 5 s, 1.0 mA, 90 s variable ITI) applied during early adolescence (PND 29–31) affected the corticosterone (CORT) response to a later restraint stress challenge in adulthood. We found that females, but not males, displayed a marginally enhanced CORT response when challenged with restraint in adulthood. To further probe intrinsic sensitivity of the HPA axis in adolescent stressed females, subsequent studies utilized exogenous CRH and ACTH challenges to probe sensitivity of the pituitary and adrenal glands respectively, demonstrating that neither gland appears to be sensitized to hormone challenge as a result of adolescent stress history in females. A final experiment examined negative feedback regulation of the HPA axis through systemic administration of dexamethasone, showing that corticosteroid receptor-mediated negative feedback mechanisms were also intact in females with a history of adolescent stress. Together, these findings report that intrinsic regulatory elements of the HPA axis are fully intact in females exposed to footshock in adolescence, and that adolescent exposure to footshock had appreciably modest long-lasting effects on HPA axis sensitivity. These findings are discussed within the general context of stress resilience and vulnerability.