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

Abstract

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.

Treatment with a serotonin-depleting regimen of MDMA prevents conditioned place preference to sex in male rats.

“…Conversely, drugs that reduce 5-HT neurotransmission by antagonizing postsynaptic 5-HT receptors or acting as agonists at 5-HT 1A autoreceptors facilitate sex behavior (Ahlenius, Larsson, & Arvidsson, 1989;Da Prada, Bonetti, Scherschlicht, & Bondiolotti, 1985;Fernandez-Guasti & Escalante, 1991). Furthermore, the administration of 5,7-dihydroxytryptamine or p-chloroamphetamine (drugs that selectively destroy 5-HT nerve terminals) also stimulates sexual behavior (Da Prada, Pieri, Keller, Pieri, & Bonetti, 1978;Fernandez-Guasti & Escalante, 1991;Sodersten, Berge, & Hole, 1978). However, it has been noted that an extensive lesion is necessary to achieve this behavioral effect (Sodersten et al, 1978).…”

“…Indeed, studies have shown that treatment of rats with drug regimens that result in increased 5-HT neurotransmission-including drugs that evoke 5-HT release, stimulate 5-HT synthesis, or inhibit 5-HT reuptake-results in a decrease in male copulatory behavior (Ahlenius & Larsson, 1991;Ahlenius, Larsson, & Svensson, 1980;Foreman, Hall, & Love, 1992). Conversely, drugs that reduce 5-HT neurotransmission by antagonizing postsynaptic 5-HT receptors or acting as agonists at 5-HT 1A autoreceptors facilitate sex behavior (Ahlenius, Larsson, & Arvidsson, 1989;Da Prada, Bonetti, Scherschlicht, & Bondiolotti, 1985;Fernandez-Guasti & Escalante, 1991). Furthermore, the administration of 5,7-dihydroxytryptamine or p-chloroamphetamine (drugs that selectively destroy 5-HT nerve terminals) also stimulates sexual behavior (Da Prada, Pieri, Keller, Pieri, & Bonetti, 1978;Fernandez-Guasti & Escalante, 1991;Sodersten, Berge, & Hole, 1978).…”

D2-Like Receptors Mediate the Expulsion Phase of Ejaculation Elicited by 8-Hydroxy-2-(di-N-propylamino)tetralin in Rats

“…However, neurotoxic lesion of 5-HT cell bodies by i.c.v. or intraraphe microinjection of 5,7-dihydroxytryptamine failed to block the facilitator effects on ejaculation of 8-OH-DPAT systemically delivered (Fernandez-Guasti and Escalante, 1991). This probably rules out the participation of cerebral 5-HT1A autoreceptors to the facilitator effect of 8-OH-DPAT on ejaculation.…”

Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine

“…Among them, the postsynaptic 5-HT 1B and 5-HT 2C receptors have been shown to inhibit ejaculation upon activation (Ahlenius and Larsson 1998;Fernandez-Guasti and Rodriguez-Manzo 1992;Foreman et al 1989;Hillegaart and Ahlenius 1998;Klint et al 1992;Watson and Gorzalka 1991), whereas activation of 5-HT 1A receptors has been shown to accelerate ejaculation (Ahlenius et al 1981;Coolen et al 1997;Fernandez-Guasti and Escalante 1991;Haensel and Slob 1997;Rehman et al 1999). …”