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) administration of imipramine or amitriptyline (10 mg/kg p.o., twice daily) on the density (Bmax) and affinity (Kd) 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 Bmax of GR (by 22-45%; both 2 and 72 h after their last dose), but did not modify the Bmax of MR and the Kd 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.
Przegaliński
E
E
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Budziszewska
B
B
D000639:Amitriptyline / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000493:pharmacokinetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D000732:Androstanols; D000928:Antidepressive Agents; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000639:Amitriptyline; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D007099:Imipramine; D003345:Corticosterone