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.
Fernández-Guasti
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Departamento de Farmacologia y Toxicologia, CINVESTAV, D. F., México.
Escalante
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D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D003307:Copulation / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010134:Fenclonine