The activation of peripheral 5-HT1A receptors can inhibit seminal vesicle contraction: An in vivo animal study

Objectives: To elucidate the differential effects of stimulating various peripheral 5-HT receptor subtypes on the contractile response of seminal vesicles (SVs) induced by electrical stimulation (ES). Methods: Male Wistar rats (aged 12-14 weeks) were prepared as our previously established model, which allows an intraarterial injection of test agents to directly act on SV. Four selective 5-HT agonists8-OH-DPAT (5-HT1A), 5-nonyloxytryptamine (5-HT1B), BW723C86 (5-HT2B), and MK-212 (5-HT2C)were injected at various concentrations (from 10^-8 to 10^-4 mmol/kg). After an injection, the SV contractile response was recorded after ES of lesser splanchnic nerve was applied. Relationships between the concentration of an agonist and its effect on SV contraction were plotted and analyzed. Results: The peripheral injection of 5-HT1A agonist had a dose-dependent inhibitory effect on SV contraction and could achieve an inhibition of >50%; the IC50 was 3.16x10^-6 mmol/kg. No significant effects were observed with the peripheral injection of 5-HT1B, 5-HT2B, or 5-HT2C agonist. Conclusions: Our in vivo animal study shows that the activation of peripheral 5-HT1A receptors can inhibit ES-induced SV contraction, whereas the activation of peripheral 5-HT1B, 5-HT2B, or 5-HT2C receptors has no significant effect. The results suggest that the peripheral 5-HT pathway is a potential therapeutic target of the treatment for premature ejaculation.