Centrally mediated ejaculatory response via sympathetic outflow in rats: role of N-methyl-D-aspartic acid receptors in paraventricular nucleus

Ejaculation is mediated by a spinal generator, which integrates inputs related to the sexual activity and coordinates sympathetic, parasympathetic, and motor outflow. Previous clinical studies indicate that primary premature ejaculation is related to the hyperactivity of the sympathetic nervous system. In this study, we explored the roles of N-methyl-D-aspartic acid (NMDA) receptors in paraventricular nucleus of the hypothalamus (PVN) on ejaculatory responses and its potential mechanism in the rats. We found that microinjection of 0.20 nmol NMDA into the PVN reduced the latency of intromission and facilitated ejaculation during copulation. Moreover, delayed ejaculation and intromission were observed after the rats were microinjected with NMDA Receptor Antagonist D (-)-2-Amino-5-phosphonopentanoic acid (AP-5). However, we discovered that microinjection of NMDA into PVN significantly increased baseline lumbar splanchnic nerve activity (LSNA), and the NMDA dose was positively correlated with the increased LSNA (r = 0.875, p = 0.04). Meanwhile, the plasma norepinephrine level in rats injected with NMDA was much higher than that in rats injected with saline (1453.4 ± 136.4 pg/mL vs. 492.3 ± 36.8 pg/mL, p < 0.01). Additionally, AP-5 reduced the baseline LSNA and abrogated the enhancing activity of NMDA in LSNA. Thus, we propose that NMDA receptors in PVN may facilitate ejaculation through enhancing the activity of sympathetic system.