Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal regulation after adrenalectomy and corticosterone replacement

Background: Previous studies have demonstrated that rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiv eness, demonstrated by increased and/or prolonged elevations of adrenocorti cotropin (ACTH) and/or corticosterone (CORT) after stress. This study inves tigated possible mechanisms of HPA hyperresponsiveness in E rats by manipul ating CORT feedback regulation of HPA activity via adrenalectomy (ADX) with or without CORT replacement. Methods: Male Sprague-Dawley rat offspring from prenatal E, pair-fed (PF) a nd ad libitum-fed control (C) groups were tested at 90 to 120 days of age. Rats were either sham-operated or underwent ADX, with or without CORT repla cement. CORT (25 mug/ml) was replaced via the drinking water to achieve bas al plasma CORT levels and maintain a phasic CORT signal. Seven days after s urgery, animals were decapitated at the diurnal peak either under basal con ditions or after a 15-min restraint stress, and trunk blood was collected. Results: After ADX, loss of the CORT feedback signal resulted in increased plasma ACTH in all groups compared with those in sham animals. In addition, under basal conditions, ADX E rats had significantly greater plasma ACTH l evels than both PF and C rats. However, no differences were seen in ADX rat s after stress. CORT replacement after ADX was partially effective in norma lizing ACTH levels under both basal and stress conditions, with no differen ces among E, PF, and C animals. Conclusions: These results suggest that E males may exhibit enhanced stimul atory inputs to the hypothalamus, increased pituitary sensitivity to secret agogues, or both, which may be revealed after ADX. In contrast, E animals s eem similar to controls in their ability to use an exogenous CORT signal to regulate HPA activity.