title: Antagonism by citalopram and tianeptine of presynaptic 5-HT1B heteroreceptors inhibiting acetylcholine release.
abstract: The interactions of citalopram and tianeptine, two antidepressants having opposite effects on serotonin (5-HT) uptake, with 5-HT1B presynaptic heteroreceptors located on cholinergic terminals were investigated. In rat hippocampal synaptosomes, citalopram (0.01 or 0.1 microM) or tianeptine (0.01-10 microM) did not modify the basal or the K(+)-evoked release of [3H]acetylcholine. Only at the concentration of 100 microM did tianeptine significantly decrease (-18%) the K(+)-evoked release of [3H]acetylcholine without affecting the spontaneous outflow of radioactivity. The inhibitory effect of 7-trifluoromethyl-4-(4-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS 12066B), a 5-HT1B receptor agonist, on the stimulation-induced release of [3H]acetylcholine was reduced in a concentration-dependent manner by citalopram and tianeptine. Both drugs completely reversed the inhibitory effects of CGS 12066B at concentrations that did not modify by themselves the release of [3H]acetylcholine. In contrast, tianeptine, up to a concentration of 1 microM, failed to antagonise the inhibitory effect of the muscarinic receptor agonist carbachol on K(+)-evoked [3H]acetylcholine release. Finally, the administration of tianeptine ex vivo (10 or 20 mg/kg) modified neither the depolarisation-induced release of [3H]acetylcholine nor the inhibitory effect of CGS 12066B on this presynaptic process. These findings further confirm that antidepressants interact in vitro with presynaptic 5-HT1B heteroreceptors.
authors.affiliation: Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Bolaños-Jiménez
authors.forename: R M
authors.initials: RM
authors.lastname: de Castro
authors.forename: G
authors.initials: G
authors.lastname: Fillion
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D011810:Quinoxalines; D011985:Receptors, Serotonin; D013841:Thiazepines; D015283:Citalopram; C050504:tianeptine; C052561:CGS 12066B; D000109:Acetylcholine; D011188:Potassium