Role of presynaptic serotonergic receptors on the mechanism of action of 5-HT1A and 5-HT1B agonists on masculine sexual behaviour: physiological and pharmacological implications.

In order to establish whether the 5-HT1A or the 5HT1B agonists, 8-OH-DPAT or TFMPP, produce their facilitatory or inhibitory actions on masculine sexual behaviour via a mechanism involving: (a) the serotonin synthesis or release; (b) the stimulation of presynaptic receptors, or (c) the stimulation of somatodendritic receptors, three series of experiments were performed. The administration of the serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 days), facilitated sexual behaviour but does not interfere neither with the inhibitory nor with the facilitatory effects of TFMPP (0.5 mg/kg) or 8-OH-DPAT (0.5 mg/kg), respectively. The icv or the intraraphé administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), slightly stimulated masculine sexual behaviour and produced a decrease in serotonin and its metabolite levels. In lesioned animals TFMPP (0.5 mg/kg) resulted in an inhibitory effect reflected as a prolongation of the ejaculation latency. The inhibitory effect of this drug on mounting behaviour was not observed in 5,7-DHT treated rats. In lesioned animals 8-OH-DPAT (0.5 mg/kg) produced the same facilitatory effect. Present data indicate that serotonergic postsynaptic receptors mediate both the inhibitory and the facilitatory actions of TFMPP or 8-OH-DPAT in copulation. All data further support the idea that endogenous serotonin acts via the stimulation of 5-HT1B receptors to induce its inhibitory effects on masculine sexual behaviour.