THE EFFECT OF LONG-TERM TREATMENT WITH ANTIDEPRESSANT DRUGS ON THE HIPPOCAMPAL MINERALOCORTICOID AND GLUCOCORTICOID RECEPTORS IN RATS

The effects of long-term (28 days) and short-term (2 days) administrat ion of imipramine or amitriptyline (10 mg/kg p.o., twice daily) on the density (B(max)) and affinity (K(d)) of mineralocorticoid (MR) and gl ucocorticoid receptors (GR) were determined in the rat hippocampus. MR and GR were examined by an in vitro [H-3]corticosterone binding to so luble molecules in the cytosol, using the selective GR agonist RU 2836 2 to discriminate between MR and GR. Long-term treatment with antidepr essant 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 M R 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 ac tivity of the hypothalamic-pituitary-adrenal axis.