Glucocorticoids in the hippocampus mediate adaptive responses elicited by stressful stimuli. In this study we investigated glucocorticoid receptor gene expression in the rat hippocampus following acute stress. A significant decrease in glucocorticoid receptor mRNA levels was observed in the hippocampus less than 1 h after the onset of stress. This decrease was inhibited by administering either MK-801, diazepam or propranolol prior to exposure to stress. The effect of diazepam on the stress-induced decrease in hippocampal glucocorticoid receptor mRNA was reversed by Ro-15-1788, suggesting that it is mediated by central benzodiazepine receptors, i.e. GABA-A. These results indicate that NMDA, GABA-A and β-adrenergic receptors are involved in the mechanism of the stress-induced decrease in glucocorticoid receptor mRNA levels in the rat hippocampus.