The effect of chronic treatment with antidepressant drugs on the corticosteroid receptor levels in the rat hippocampus.
The effect of long-term (28 days) treatment with desipramine, (+)-oxaprotiline (selective inhibitors of the noradrenaline - NA - uptake), citalopram (a selective inhibitor of the serotonine - 5-HT - uptake) and mianserin (an atypical antidepressant drug, devoid of an effect on the monoamine uptake) on the binding parameters of corticosteroid receptors was studied in the rat hippocampus. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [3H]-corticosterone binding in the cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to discriminate between MR and GR. Long-term treatment with desipramine significantly increased the Bmax of GR at both 2 (increase by 42%) and 72 h (increase by 27%) after its last dose, but did not change the Bmax of MR and the Kd of GR and MR. Repeated treatment with (+)-oxaprotiline, citalopram and mianserin did not modify the binding parameters of GR and MR. These results indicate that the ability to increase the Bmax of GR is not a common feature of all antidepressant drugs, and that the influence of antidepressant drugs on the GR level is not connected with their action on the uptake of NA or 5-HT.
Budziszewska
B
B
Department of Endocrinology, Polish Academy of Sciences, Kraków.
Siwanowicz
J
J
Przegaliński
E
E
D000704:Analysis of Variance; D000732:Androstanols / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001667:Binding, Competitive; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008376:Maprotiline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008803:Mianserin / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology
D000732:Androstanols; D000928:Antidepressive Agents; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D012702:Serotonin Antagonists; D015283:Citalopram; D008803:Mianserin; D008376:Maprotiline; C027299:hydroxymaprotilin; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003891:Desipramine; D003345:Corticosterone; D009638:Norepinephrine