The effect of long-term treatment with antidepressant drugs on the hippocampal mineralocorticoid and glucocorticoid receptors in rats

Abstract

The effects of long-term (28 days) and short-term (2 days) administration of imipramine or amitriptyline (10 mg/kg p.o., twice daily) on the density ( B max) and affinity ( K d) of mineralocorticoid (MR) and glucocorticoid receptors (GR) were determined in the rat hippocampus. MR and GR were examined by an in vitro [ 3H]corticosterone binding to soluble molecules in the cytosol, using the selective GR agonist RU 28362 to discriminate between MR and GR. Long-term treatment with antidepressant drugs significantly increased the B max of GR (by 22–45%; both 2 and 72 h after their last dose), but did not modify the B max of MR and the K d of GR and MR. The above data suggest that up-regulation of GR may be involved in the effect of antidepressant drugs on the activity of the hypothalamic-pituitary-adrenal axis.