The glucocorticoid receptor antagonist mifepristone reduces ethanol intake in rats under limited access conditions.

There is a substantial amount of evidence indicating control over ethanol intake by steroid hormones, particularly adrenal glucocorticoids. Thus far, however, studies employing pharmacological methods have failed to find effects of glucocorticoid receptor blockade on voluntary ethanol consumption. Since length of ethanol access period can influence ethanol consumption levels as well as potential pharmacological effects in such studies, the present study was conducted to determine the effects of acute administration of the glucocorticoid receptor (GR) antagonist mifepristone on voluntary ethanol intake under limited access conditions. Rats were fluid restricted and given concurrent access to 10% ethanol and water in a two-bottle choice paradigm for 1 h/day, 5 days a week. Both fluids were available ad libitum during the remaining 2 days per week. Administration of mifepristone (1, 5 and 20 mg/kg i.p.) immediately prior to the limited access two-bottle access period dose-dependently suppressed ethanol intake (maximum 40% at 20 mg/kg). The mineralcorticoid receptor (MR) antagonist spironolactone (10, 25 and 50 mg/kg i.p.) was without effect on ethanol intake, and neither compound had an effect on water intake. These data confirm an active role of GRs in modulating voluntary ethanol consumption, particularly under conditions of limited access.