Glucocorticoids antagonize the sedative action of ethanol in mice

The effect of corticosterone on sleep time in mice following a hypnotic dose of ethanol (3 g/kg) was determined. An acute dose of the steroid (10 mg/kg) administered 15 min prior to ethanol injection significantly shortened the sleep time (by 55%). Brain levels of ethanol were not affected by the steroid treatment. The effect was specific to glucocorticoids because steroids without glucocorticoid activity including testosterone and 17 beta-estradiol were ineffective. These results indicate that glucocorticoids have an antagonistic effect to the acute action of ethanol in the brain. The rapid onset of the corticosterone action in antagonizing ethanol-induced sedation suggests that the action is mediated by a membrane mechanism rather than the classical steroid mechanism involving an intracellular receptor and gene expression.