Sensitivityin vivo of central? 2-and opiate receptors after chronic treatment with various antidepressants

Abstract

Recent studies suggest that the antidepressant activity could be explained by gradually developing modifications in the sensitivity of some central monoaminergic receptors. As concernsα ₂-receptors, some largely indirect informations suggest that a subsensitivity develops following chronic treatment with desipramine or imipramine. However it is not clear whether this effect is shared by other antidepressants. In view of the important role of these receptors in the regulation of noradrenergic neurotransmission, single cell recording and microiontophoretic techniques were used in this work to systematically assess locus coeruleus (L.C.)α ₂-receptor sensitivity following acute and chronic administration of various antidepressants. The responsiveness of L.C.α ₂-receptors to iontophoretically applied clonidine was studied simultaneously with the responsiveness of L.C. opiate receptors to iontophoretically applied morphine in order to test the specificity in the putative modifications induced by the antidepressants. The compounds studied were desipramine (DMI), imipramine (IMI), clomi-pramine (CIMI), zimelidine (ZIM), mianserin (MIAN), iprindole (IPR) and chlorpromazine (CPZ). Long-term treatment with DMI, IMI and ZIM but not with the other clinically effective antidepressant drugs induced a decrease in the responsiveness of L.C. neurons to iontophoretically applied clonidine. None of the drugs tested altered the responsiveness of these neurons to iontophoretically applied morphine. Consequently the therapeutic effectiveness of antidepressant drugs can not be generally related to modulation of the sensitivity of centralα ₂ or opiate receptors.