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Effects of mineralocorticoid and glucocorticoid receptor blockade on hypothalamic-pituitary-adrenal function in female rats prenatally exposed to ethanol.

BACKGROUND
Rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness, demonstrated by increased and/or prolonged elevations of adrenocorticotropic hormone (ACTH) and/or corticosterone (CORT) in response to stressors. The present study examined the possible role of CORT feedback deficits in mediating this hyperresponsiveness by examining HPA function following mineralocorticoid (MR) and glucocorticoid (GR) receptor blockade.


METHODS
Adult female Sprague-Dawley offspring from E, pair-fed (PF), and control (C) groups were injected subcutaneously with the MR antagonist spironolactone (SPIRO; 30 mg/kg bw), the GR antagonist RU38486 (120 mg/kg bw), or vehicle. One hour postinjection, blood samples (0 minutes) were taken via jugular cannulae to obtain a measure of prestress ACTH and CORT levels. Rats were then loosely restrained for 1 hour, and samples were taken during (15, 30, and 60 minutes) and then 1 hour following stress, for determination of plasma ACTH and CORT levels.


RESULTS
Both SPIRO and RU38486 significantly increased prestress ACTH levels in E compared with both PF and C females. In contrast, RU38486 significantly increased ACTH levels in C compared with PF females during stress and in C compared with E females during recovery. CORT levels were increased during stress in E females in response to SPIRO, and RU38486 increased the CORT response during stress in PF and during recovery in E and PF females compared with vehicle.


CONCLUSIONS
E females showed enhanced HPA responses to both MR and GR blockade compared with PF and C before restraint as well as a different pattern of responsivity during and following restraint. While receptor blockade had some effect on CORT responses in PF females, changes in ACTH appear specific to ethanol. These findings suggest that the balance between HPA drive and feedback may be altered in E compared with C females.