Participation of 5‐HT_1B receptors in the inhibitory actions of serotonin on masculine sexual behaviour of mice: pharmacological analysis in 5‐HT_1B receptor knockout mice

Abstract

1 The role of the 5-Hydroxytryptamine(1B) (5-HT(1B)) receptor subtype in masculine sexual behaviour in mice was analysed in both 5-HT(1B) receptor knockout (KO(1B)) and wild-type (WT) animals. 2 Comparison of male copulatory behaviour of WT and KO(1B) strains revealed that KO(1B) mice become interested earlier in sexual behaviour, but require more stimulation to achieve ejaculation than its corresponding WT strain. 3 The pharmacological manipulation of male sexual activity in the WT strain showed that the serotonin precursor 5-Hydroxytryptophan (5-HTP), the 5-HT(1B) agonist (1-(m-trifluoromethylphenyl) piperazine (TFMPP) and the 5-Hydroxytryptamine(1A) (5-HT(1A)) receptor agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT) all inhibited male copulatory behaviour in mice. 4 In KO(1B) mice, TFMPP lacked an effect, 5-HTP exerted a mild inhibitory effect while 8-OH-DPAT provoked only a tendency towards a reduction in the percentage of animals that achieved ejaculation. In general, KO(1B) mice were less sensitive to the inhibitory actions of 5-HTP and 8-OH-DPAT than the WT strain. 5 Based on these results, we can suggest that serotonin plays a general inhibitory role in the sexual behaviour of male mice and that both 5-HT(1B) and 5-HT(1A) receptor subtypes participate in the inhibitory actions of this neurotransmitter. 6 The absence of the 5-HT(1B) receptor subtype affected both components of mouse masculine sexual behaviour, motivation and execution, further confirming the involvement of this receptor subtype in the control of this behaviour. In addition, the diminished sensitivity to serotonergic stimulation exhibited by KO(1B) mice suggests the occurrence of compensatory changes as a consequence of the absence of the 5-HT(1B) receptor subtype.

Effects of systemic and intra-nucleus accumbens 5-HT2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats

“…Data shown are means±SEM expressed as a percentage of baseline performance. *Denotes significance from control at p<0.05 following Newman-Keuls post hoc tests mediated (Kennett and Curzon 1988a;Rodriguez-Manzo et al 2002;Schechter 1988). As activation of the 5-HT 1B receptor has also been shown to increase M50 values in lateral hypothalamic and VTA ICSS experiments (Harrison et al 1999;Hayes et al 2006), the present results demonstrating an attenuation of TFMPP's effects by SB 242084 provide evidence that TFMPP's effects on VTA ICSS are largely 5-HT 2C receptor-mediated.…”

Analysis of sexual behaviour in male rabbits across successive tests leading to sexual exhaustion

“…Accordingly, the simultaneous injection of haloperidol, a nonspecific dopamine receptor antagonist, blocks the ability of these drugs to reverse sexual satiety (Rodriguez-Manzo, 1999b). Serotonin, in contrast, tends to inhibit male sexual behaviour in rats (Fernandez-Guasti and Rodriguez-Manzo, 1992) and mice (Rodriguez-Manzo et al, 2002): injection of 5-HTP, a serotonin precursor, increases the number of mounts and intromissions preceding ejaculation, prolongs the intromission and ejaculation latencies, and increases the post-ejaculatory interval. However, the injection of 8-OH-DPAT, a potent agonist of 5-HT 1A receptors, promotes ejaculation or reverses sexual exhaustion (Fernandez-Guasti and Rodriguez-Manzo, 1997;Rodríguez-Manzo and Fernández-Guasti, 1994).…”

Sexual behavior in male rodents

“…Serotonergic 5-HT 1A agonists − Mice: (Rodriguez-Manzo et al, 2002;Popova and Amstislavskaya, 2002) 5-HT 1B knockout mice were less impaired by serotonergic drugs, but needed more stimulation to ejaculate, possibly because of compensatory mechanisms (Rodriguez-Manzo et al, 2002).…”