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

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. 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. 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. 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. 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. 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.British Journal of Pharmacology (2002) 136 , 1127–1134. doi: 10.1038/sj.bjp.0704827