Variations in Corticosterone Feedback Do Not Reveal Differences in HPA Activity After Prenatal Ethanol Exposure

Abstract

Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors in adult animals. Possible mechanisms mediating this alteration in HPA responsiveness include stress-associated changes in corticosterone (CORT) feedback signals, alterations in CORT signals under basal conditions, and CORT-independent mechanisms. We examined the effects of adrenalectomy (ADX) and CORT replacement with a constant, low-level CORT signal via CORT/cholesterol pellets on HPA responses to restraint stress. Adult Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups underwent sham ADX (sham), ADX without CORT replacement, or ADX with CORT replacement. Animals were tested during the trough of the circadian rhythm. In the sham condition, E females showed increased adrenocorticotropin hormone (ACTH) and CORT responses to restraint stress compared with C females. Basal and stress-induced ACTH levels were significantly increased in ADX compared with sham animals across all prenatal groups. Constant CORT replacement reduced basal ACTH levels compared with levels in the ADX group, although levels were still increased compared with those observed in the sham group. CORT replacement was minimally effective at reducing ACTH levels during stress. Although the effects of ADX may have masked possible influences of circadian drive or prenatal group, these findings suggest that in the absence of a CORT feedback signal or in the presence of a constant, low-level CORT feedback signal, E, PF, and C animals do not differ in their abilities to regulate ACTH secretion during the trough of the circadian rhythm.