title: Changes in the rat brain 5-HT1A and 5-HT2 receptors after chronic administration of levoprotiline, (+)-oxaprotiline and other antidepressant drugs.
abstract: The effects of levoprotiline (LEV), a (-)-enantiomer of oxaprotiline (OXA) and a clinically effective antidepressant, on the binding parameters of hippocampal 5-HT1A and cortical 5-HT2 receptors of rats were compared with those of (+)-enantiomer of OXA ((+)-OXA), imipramine and mianserin. Both LEV and (+)-OXA displayed in vitro some affinity for 5-HT1A receptors labelled with [3H]-8-OH-DPAT, and for 5-HT2 receptors labelled with [3H]-ketanserin. Repeated administration of LEV, for 14 days led to a marked increase in the number of 5-HT1A binding sites in the rat hippocampus, with no change in the KD values. (+)-OXA, imipramine and mianserin produced similar effects on 5-HT1A binding parameters. The number of 5-HT2 receptors was increased after two weeks of LEV administration, not altered after (+)-OXA, and decreased after imipramine or mianserin. The number of [3H]-ketanserin binding sites was decreased after four weeks of (+)-OXA administration, but not altered after LEV. The specific binding of [3H]-ketanserin in the rat cerebral cortex was decreased after repeated treatment with LEV and (+)-OXA (ex vivo). In competition studies the affinity of serotonin for [3H]-ketanserin binding sites was decreased in LEV- and increased in (+)-OXA-treated rats. The results suggest that LEV similarly to other antidepressants increases the number of 5-HT1A receptors, however without common alteration in 5-HT2 receptor number and function.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors.forename: V
authors.initials: V
authors.lastname: Klimek
authors.forename: J
authors.initials: J
authors.lastname: Zak-Knapik
authors.forename: C
authors.initials: C
authors.lastname: Cannizzaro
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008376:Maprotiline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D008803:Mianserin; D008376:Maprotiline; C027299:hydroxymaprotilin; D007099:Imipramine