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.

Figure 1

Spontaneous sexual behaviour of sexually experienced WT (n=78, filled bars) and KO_1B (n=92, empty bars) mice on two consecutive testing sessions. (A) Percentage of animals that showed mounts (M), intromissions (I) and ejaculation (E) in each session. (B) Latencies to the occurrence of the first mount (ML) or intromission (IL) and to achievement of ejaculation (EL) in an ejaculatory series expressed as mean±s.e.mean. (C) Median number of mounts (M), intromissions (I) and total mount events (TME, M+I) that preceded ejaculation. (A) Chi square test, ^**P<0.02, (B and C) Mann Whitney U test ^*P<0.05; ^**P<0.02, ^***P<0.001.

Figure 2

Percentage of KO_1B (right columns) and WT (left columns) male mice showing mounts (M), intromissions (I) and ejaculation (E) after treatment with different doses of either 5-HTP (A; n=10 for WT, n=8 for KO_1B); TFMPP (B; n=18 for WT; n=10 for KO_1B) or 8-OH-DPAT (C; n=10 for both WT and KO_1B). Cochran Q ANOVA followed by the binomial test. ^*P<0.05; ^**P<0.002; ^***P<0.001. S, saline; CD, carbidopa (25 mg kg⁻¹).