Objectives:To investigate the effects of insulin replacement on ejaculatory dysfunction in streptozotocin (STZ)-induced diabetic rats. Methods: Rats were divided into three groups: (i) STZ-treated group; (ii) STZ-treated + insulin replacement (5 and 2 international units [IU]) group; and (iii) control group. The ejaculatory function in rats was evaluated using the spontaneous seminal emission (SSE) test. The amount of seminal vesicle fluid (SVF) stored in seminal vesicle was measured after the SSE test. Blood glucose was measured using a simplified blood glucose meter. Results: In the SSE test, the ejaculatory capacity in STZ-induced diabetic rats deteriorated with time after the onset of diabetes, and the incidence of SSE and the amount of ejaculated seminal material (SM) were significantly decreased from 5 weeks after STZ administration. Likewise, the amount of SVF was also significantly decreased in a time-dependent manner. One week after STZ administration when ejaculatory capacity had not yet diminished , insulin replacement (for 4 weeks) completely prevented the decrease in frequency of SSE, the amount of SM and SVF. However, insulin replacement after the dysfunction had occurred (5 or 15 weeks after STZ administration) did not allow all parameters for ejaculatory function to be restored to the levels of the control group. Conclusion: This study demonstrates that at an early stage following the onset of diabetes, insulin replacement can prevent ejaculatory dysfunction in STZ-induced diabetic rats, but once the dysfunction occurs, treatment with insulin alone does not restore the ejaculatory capacity to normal levels. In addition, this study suggests that the loss of seminal emission that results from a decrease in SVF may be involved in the mechanism of ejaculatory dysfunction in diabetic rats.

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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,