Short-term administration of fluoxetine and venlafaxine decreases corticosteroid receptor mRNA expression in the rat hippocampus

Chronic treatment with antidepressant drugs (2 weeks or longer) increases c orticosteroid receptor mRNA expression in the hippocampus and reduces hypot halamic-pituitary-adrenal axis activity in parallel with improving mood and neuroendocrine function. Earlier effects are less well documented. We exam ined the effects of short term (9 days) treatment with fluoxetine (10 mg/kg ) and venlafaxine (10 mg/kg) on hippocampal mineralocorticoid receptor (MR) and glucocorticoid receptor(GR) mRNA expression and spatial memory in adul t rats. In situ hybridization histochemistry showed that the antidepressant s decreased MR mRNA expression in all hippocampal subregions (e.g. 45% decr ease in CA1 with venlafaxine, P < 0.001), while GR mRNA expression was sele ctively reduced in the CA3 subregion. There was a trend for decreased plasm a corticosterone levels following fluoxetine (50% fall, P = 0.07) and venla faxine (30% fall, P = 0.18) but neither antidepressants affected spatial me mory in the watermaze. Thus antidepressants can have complex and opposing a ctions on hippocampal corticosteroid receptor expression depending on the d uration of treatment. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.