Synergistic actions of apomorphine and m-chlorophenylpiperazine on ejacu-lation, but not penile erection in rats

摘要

It has been suggested that dopamine (DA) and serotonin (5-HT) and their receptors, particularlyD2-like and 5-HT2C receptors, may play a significant role in the control of male sexual function.The purpose of this study was to investigate whether the combination of a dopamine receptor ago-nist apomorphine and a 5-HT2 receptor agonist m-CPP would potentiate penile erection and ejacu-lation in male rats. Systemic administration of either apomorphine (0.01-0.1 mg/kg, s.c.) orm-CPP (0.01-0.3 mg/kg, i.p.) dose-dependently elicited penile erections, but did not induce ejacu-lation. When combined, there was a drastic increase in both the incidence of ejaculation and theamount of ejaculated seminal materials, while the proerectile effect induced by each drug was notpotentiated. The proejaculatory effect induced by the combination of apomorphine (0.1 mg/kg, s.c.)and m-CPP (0.3 mg/kg, i.p.) was completely blocked by pretreatment with the D2-like receptor an-tagonists haloperidol and sulpiride, but not by the D,-like receptor antagonist SCH-23390. Thesynergistic action for ejaculation was also blocked by domperidone, the D2-like receptor antago-nist that dose not cross the blood-brain barrier. The rats pretreated with the 5-HT2C receptor antag-onist SB242084 did not show the synergistic action by the combination of apomorphine andm-CPP, whereas the rats pretreated with the 5-HT2A receptor antagonist ketanserin and the 5-HT2Breceptor antagonist SB204741 showed the combination-induced synergistic action. These resultssuggest that the combination of a small dose of apomorphine and m-CPP potently and selectivelyfacilitates the ejaculatory response through the activation of D2-like and 5-HT2C receptors, respec-tively. The D2-like receptors involved in the synergistic action may be, at least in part, located inthe peripheral sites.