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 D(2)-like and 5-HT(2C) 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-HT(2) 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 D(2)-like receptor antagonists haloperidol and sulpiride, but not by the D(1)-like receptor antagonist SCH-23390. The synergistic action for ejaculation was also blocked by domperidone, the D(2)-like receptor antagonist that dose not cross the blood-brain barrier. The rats pretreated with the 5-HT(2C) receptor antagonist SB242084 did not show the synergistic action by the combination of apomorphine and m-CPP, whereas the rats pretreated with the 5-HT(2A) receptor antagonist ketanserin and the 5-HT(2B) 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 D(2)-like and 5-HT(2C) receptors, respectively. The D(2)-like receptors involved in the synergistic action may be, at least in part, located in the peripheral sites.
Yonezawa
Akihiko
A
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Sendai. florina@mail.cytspb.rssi.ru
Yoshizumi
Masaru
M
Ise
Shin-Nosuke
SN
Watanabe
Chizuko
C
Mizoguchi
Hirokazu
H
Furukawa
Katsuo
K
Tsuru
Hiromichi
H
Kimura
Yukio
Y
Kawatani
Masahito
M
Sakurada
Shinobu
S
D000818:Animals; D001058:Apomorphine / Q000819:agonists* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004542:Ejaculation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000819:agonists* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018491:Dopamine Agonists; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D001058:Apomorphine; C015068:1-(3-chlorophenyl)piperazine