Effects of quipazine on pre- and postsynaptic serotonin receptors: single cell studies in the rat CNS

Many behavioural and biochemical studies have pointed to an agonistic activity of quipazine on serotonin (5-HT) receptors. In the present electrophysiological study, the effect of quipazine on pre- and postsynaptic 5-HT receptors in the rat was studied. Quipazine, administered intravenously, depressed the firing rate of 5-HT-containing dorsal raphe neurones (ED50 = 0.82 mg/kg). Microiontophoretic applications of quipazine on 5-HT-containing neurones in the dorsal raphe and on neurones of two forebrain regions receiving a 5-HT input (the ventral lateral geniculate nucleus and the dorsal hippocampus) consistently depressed neuronal firing rate as did 5-HT and D-lysergic acid diethylamide (LSD). Quipazine was more potent on 5-HT neurones than on the ventral lateral geniculate nucleus and hippocampal neurones: the post/presynaptic efficacy ratio for quipazine was similar to that of LSD. Following a selective denervation of 5-HT neurones with intraventricular injection of 5,7-di-hydroxy-tryptamine in desipramine-pretreated rats, the responsiveness of neurones in the ventral lateral geniculate nucleus to quipazine, applied microiontophoretically, was increased as was that to 5-HT and to LSD. These results provide direct evidence for the agonistic activity of quipazine on both pre- and postsynaptic 5-HT receptors.