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

Abstract

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.Ejaculation is defined as a complex physiological process that results in the expulsion of the seminal fluid from the urethral meatus (19,22). This process consists of three distinct phenomena: seminal emission (secretion of the mixed fluids composing semen into the posterior urethra), ejaculation (expulsion of semen from the posterior urethra to the outside), and bladder neck closure. These events occur reflexively, and require coordination of autonomic and somatic nervous systems (7, 9, 16) in order to achieve effective delivery of semen. A variety of neurotransmitters distributed in supraspinal and spinal sites are important for the controling ejaculation. Among the several neurotransmitters, it has been suggested that the dopaminergic and serotonergic systems have both excitatory and inhibitory influences on penile erection and ejaculation at the supraspinal level (10,

Guibourtia tessmannii -induced fictive ejaculation in spinal male rat: involvement of D 1 , D 2 -like receptors

“…In a normal condition, these events occur reflexively, and require coordination of autonomic and somatic nervous system in order to achieve effective delivery of semen (Grillner 1985 ; Giuliano & Clement 2005 ; Yonezawa et al. 2009 ; Gajjala & Khalidi 2014 ; Huang et al. 2016 ; Kozyrev et al.…”

Neurophysiology of Erection and Ejaculation

“…For example, selective agonists of dopamine receptor subtype‐1 elicit erection, whereas activation of dopamine receptor subtypes‐2 and ‐3 trigger ejaculation [27,32–34]—even in anesthetized rats and in absence of sexual stimuli [35]. Experimental data also suggest that a combination of a nonselective dopamine receptor agonist (apomorphine) and a serotonin (5‐HT) receptor agonist (m‐CPP) facilitates the ejaculatory response via dopamine subtype‐2 and 5‐HT 2c receptors [36].…”