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

It has been suggested that dopamine (DA) and serotonin (5-HT) and their receptors, particularly D2-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 agonist apomorphine and a 5-HT2 receptor agonist m-CPP would potentiate penile erection and ejaculation in male rats. Systemic administration of either apomorphine (0.01-0.1 mg/kg, s.c.) or m-CPP (0.01-0.3 mg/kg, i.p.) dose-dependently elicited penile erections, but did not induce ejaculation. When combined, there was a drastic increase in both the incidence of ejaculation and the amount of ejaculated seminal materials, while the proerectile effect induced by each drug was not potentiated. 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 antagonists haloperidol and sulpiride, but not by the D1-like receptor antagonist SCH-23390. The synergistic action for ejaculation was also blocked by domperidone, the D2-like receptor antagonist that dose not cross the blood-brain barrier. The rats pretreated with the 5-HT2C receptor antagonist SB242084 did not show the synergistic action by the combination of apomorphine and m-CPP, whereas the rats pretreated with the 5-HT2A receptor antagonist ketanserin and the 5-HT2B receptor antagonist SB204741 showed the combination-induced synergistic action. These results suggest that the combination of a small dose of apomorphine and m-CPP potently and selectively facilitates the ejaculatory response through the activation of D2-like and 5-HT2C receptors, respectively. The D2-like receptors involved in the synergistic action may be, at least in part, located in the peripheral sites.