ANTAGONISM BY CITALOPRAM AND TIANEPTINE OF PRESYNAPTIC 5-HT(1B) HETERORECEPTORS INHIBITING ACETYLCHOLINE-RELEASE

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 muM) or tianeptine (0.01-10 muM) did not modify the basal or the K+-evoked release of [H-3]acetylcholine. Only at the concentration of 100 muM did tianeptine significantly decrease (- 18%) the K+-evoked release of [H-3]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 [H-3]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 [H-3]acetylcholine. In contrast, tianeptine, up to a concentration of 1 muM, failed to antagonise the inhibitory effect of the muscarinic receptor agonist carbachol on K+-evoked [H-3]acetylcholine release. Finally, the administration of tianeptine ex vivo (10 or 20 mg/kg) modified neither the depolarisation-induced release of [H-3]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.