A role for peripheral 5-HT2 receptors in serotonin-induced facilitation of the expulsion phase of ejaculation in male rats.

Introduction: The urethrogenital reflex (UGR) is used as a physiological animal model of the autonomic and somatic activity that accompanies ejaculatory-like reflexes (ELRs). Serotonin (5-HT) plays an important role in regulating ejaculation.

Aim: To examine the effects of intraurethral 5-HT on ELRs and to examine the effects of various 5-HT receptor subtypes on the 5-HT-induced changes in the ELRs.

Methods: The effects of intraurethral infusion of 5-HT on ELRs were examined by monitoring the urethrogenital reflex in male rats. The effects of various 5-HT receptor-specific antagonists on the 5-HT-induced responses were examined.

Main Outcome Measures: Main outcome measures were urethral pressure threshold required to elicit the UGR and bulbospongiosus activity or ELRs.

Results: Intraurethral infusion of 5-HT (10-1,000 μM) produced a dose-dependent facilitation of the UGR, i.e., decrease in threshold urethral perfusion pressure and an increase in number of ELRs. The 5-HT3 receptor antagonists tropisetron (1 and 3 mg/kg, i.v.) and ramosetron (0.1 and 1 mg/kg, i.v.), the 5-HT7 receptor antagonist SB269970 (3 mg/kg, i.v.), and the 5-HT1 A receptor antagonist WAY-100635 (1 mg/kg, i.v.) all failed to inhibit 5-HT-induced facilitation of the UGR. However, ritanserin (1 mg/kg, i.v.), a nonselective 5-HT2 receptor antagonist, and xylamidine (0.01-1 mg/kg, i.v.), a peripherally restricted nonselective 5-HT2 receptor antagonist, significantly inhibited both the decrease in urethral pressure threshold and the increase in number of ELRs induced by intraurethral infusion of 5-HT.

Conclusion: These results suggest that in the male rat urethra, peripheral 5-HT2 receptors are involved in the 5-HT-induced facilitation of the expulsion phase of ejaculation.