The antiglucocorticoid RU486 inhibits the ethanol-induced increase of tryptophan oxygenase

The effect of the glucocorticoid-antagonist RU486 (Roussel-Uclaf, France) on the increased activity of hepatic tryptophan oxygenase (TO) after administration of corticosterone and ethanol in rats was studied. RU486 (40 mg/kg per os) inhibited completely the effect of corticosterone (5-15 mg/kg injected intraperitoneally) on TO. Ethanol (4 g/kg) given intraperitoneally is followed by peak corticosterone concentrations comparable to those seen after the administration of 5-10 mg exogenous corticosterone, and increased the TO activity 3-fold 4 h after the injection. RU486 inhibited completely the ethanol-induced increase of TO, indicating that this increase is mediated by corticosterone.