• Natalie Kozyrev, Michael N Lehman, and Lique M Coolen.
• University of Michigan, Department of Molecular and Integrative Physiology, Ann Arbor, MI 48109, USA.
• J Sex Med. 2012 May 1; 9 (5): 1303-18.

IntroductionEjaculation is a complex reflex mediated by a spinal ejaculation generator located in the lumbosacral spinal cord and consisting of a population of lumbar spinothalamic (LSt) neurons. LSt neurons and their intraspinal axonal projections contain several neuropeptides, including gastrin-releasing peptide (GRP).AimTo test the hypothesis that GRP is critically involved in mediating ejaculation by acting in autonomic and motor areas of the lumbosacral spinal cord, utilizing a physiological paradigm to investigate ejaculatory reflexes in isolation of supraspinal inputs.MethodsDual immunohistochemistry for GRP and galanin was performed to investigate co-expression of GRP in LSt cells of control male rats. Next, anesthetized, spinalized male rats received intrathecal infusions of either GRP antagonist RC-3095 (0, 10, or 20 nmol/10 µL) or GRP (0, 0.2, 0.5 nmol/10 µL). Ejaculatory reflexes were induced by electrical stimulation of the dorsal penile nerve (DPN) which reliably triggers rhythmic increases in seminal vesicle pressure (SVP) and contractions of the bulbocavernosus muscle (BCM), indicative of the emission and expulsion phases of ejaculation, respectively.Main Outcome MeasuresGRP in LSt cells was expressed as percentages of co-expression. SVP and electromyographic recording (EMG) of BCM activity following drug treatment and DPN stimulation were recorded and analyzed for numbers of SVP increases, BCM events and bursts.ResultsGRP was exclusively expressed in LSt cells and axons. Intrathecal infusion of RC-3095, but not saline, blocked SVP increases and BCM bursting induced by DPN stimulation. Intrathecal infusions of GRP, but not saline, triggered SVP increases and BCM bursting in 43-66% of animals and facilitated SVP increases and BCM bursting induced by subthreshold DPN stimulation in all animals.ConclusionThese data support a critical role for GRP for control of the emission and expulsion phases of ejaculation in male rats by acting in LSt target areas in the lumbosacral spinal cord.© 2012 International Society for Sexual Medicine.

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