Activation of mu or delta opioid receptors in the lumbosacral spinal cord is essential for ejaculatory reflexes in male rats.

Natalie Kozyrev,Lique M Coolen,David Brown

doi:10.1371/journal.pone.0121130

Abstract

Ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.

Highlights

Ejaculation is a complex physiological phenomenon that is highly rewarding and culminates in the ejection of seminal contents from the urethral meatus [1,2,3]
Post hoc analyses revealed that animals treated with either dose of CTOP during the testing trial 2, i.e. drug trial, had significantly decreased bulbocavernosus muscle (BCM) events in response to 30 or 60 Hz dorsal penile nerve (DPN) stimulation compared to their DPN stimulation induced BCM events following saline treatment in the first control testing trial (trial 1; 60 Hz: P
Antagonist studies showed that activation of either mu or delta opioid receptors is critical for the emission and expulsion phases of ejaculation in response to sensory stimulation in male rats

Summary

Introduction

Ejaculation is a complex physiological phenomenon that is highly rewarding and culminates in the ejection of seminal contents from the urethral meatus [1,2,3]. The spinal ejaculation generator consists of a set of interneurons in lamina 10 and the medial portion of lamina 7 of lumbar segments 3 and 4 (L3-4) that are integral in the control of ejaculation These lumbar interneurons are referred to as lumbar spinothalamic (LSt) cells due to their anatomical position in the lumbar spinal cord and projections to the subparafascicularparvocellular nucleus of the thalamus [17,18,19,20]. LSt cells display neural activation with ejaculation but not with other components of sexual behavior following copulation [20] or following electrical stimulation of the dorsal penile nerve (DPN) in male rats [14]. LSt cells have axonal projections to LSt target regions including preganglionic sympathetic, parasympathetic and motor neurons in the thoracolumbar and lumbosacral spinal cord [12,17, 21,22,23,24]

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