Possible involvement of the septo-hippocampal cholinergic and raphe-hippocampal serotonergic activations in the penile erection induced by fenfluramine in rats.

Fenfluramine (0.1-10 mg/kg, i.p.) induced penile erection in naive rats with a bell-shaped dose response curve. The response to fenfluramine (1 mg/kg) was antagonized by scopolamine (0.032-1 mg/kg) but not by methyl-scopolamine (0.032-1 mg/kg) pre-treatment. The septo-hippocampal cholinergic deafferentations by medial septum lesion or fimbria-fornix transection also attenuated the penile erection induced by fenfluramine, whereas dopaminergic blockade by sulpiride (3.2-100 mg/kg) had hardly any effect. Pindolol (0.1-3.2 mg/kg), a 5-HT1 antagonist, and ICS205-930, a 5-HT3 antagonist, but not ketanserin, a 5-HT2 antagonist, inhibited the penile erection induced by fenfluramine. Depletion of 5-HT not only by systemic injections of p-chlorophenylalanine (150 mg/kg i.p. at 72, 48 and 24 h before the test) but also by the injections of 5,7-dihydroxytryptamine (5,7-DHT), a serotonergic neurotoxin, into the median- and dorsal-raphe nuclei significantly attenuated the fenfluramine-induced penile erections. Neurochemical analyses revealed that the raphe-lesion significantly reduced the contents of serotonin (5-HT) and its major metabolite, 5-hydroxyindole acetic acid (5-HIAA) but not choline acetyltransferase (ChAT) activities in all the cortical and subcortical regions examined. The results suggest that fenfluramine facilitates the expression of penile erection in rats through an activation of the septo-hippocampal cholinergic pathway as a consequence of excitation of the raphe-hippocampal serotonergic pathway in which 5-HT1 and/or 5-HT3 receptors appear to play a regulatory role.