Spinal control of erection by glutamate in rats

Abstract

/ ajpregu.00645.2003.-The lumbosacral spinal network controlling penile erection is activated by information from peripheral and supraspinal origins. We tested the hypothesis that glutamate, released by sensory afferents from the genitals, activates this proerectile network. In anesthetized intact and T8 spinalized (i.e., freed from supraspinal inhibition) male rats, the parameters of electrical stimulation of the dorsal penile nerve (DPN) that elicited intracavernous pressure (ICP) rises were determined. In T8 spinalized rats, DPN stimulations were applied in the presence of D(Ϫ)-2-amino-5-phosphonopentanoic acid (D-AP5), a competitive NMDA receptor antagonist, or of 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX), an AMPA-kainate receptor antagonist, injected intrathecally at the lumbosacral level. Both antagonists, alone or in combination, dose dependently decreased the ICP rise and increased its latency. In conscious rats, reflexive erections were depressed by D-AP5 and NBQX, as revealed by an increased latency of the first erection and by decreases of the number of rats displaying erections, of the number of erection clusters and of the number of erections per cluster. In anesthetized rats, the combined administration of the glutamatergic agonists NMDA and AMPA elicited ICP rises in the absence of DPN stimulation. In contrast, both agonists moderately decreased the ICP rise elicited by DPN stimulation but did not affect its latency. These results support our hypothesis that glutamate, released on stimulation of the genitals and acting at AMPA and NMDA receptors, is a potent activator of the spinal proerectile network. urogenital; sexual reflexes; lumbosacral spinal cord ERECTION IS CAUSED by the simultaneous increase of blood flow to the penis and active relaxation of the erectile tissue of the corpora cavernosa and the corpus spongiosum (1). Both mechanisms are controlled by the autonomic nervous system.In conscious rats, retraction of the penile sheath elicits reflexive erections (14, 32) that are accompanied by penile pressure rises (5, 33). In anesthetized rats, intracavernous pressure (ICP) rises are reflexively elicited by stimulation of the dorsal penile nerve (DPN) (27,29,35). Reflexive erections rely on a reflex loop that includes a network of lumbosacral spinal neurons as a link between the DPN as the afferent limb and the sacral parasympathetic outflow as the efferent limb. The DPN conveys sensory information from the penis and perigenital skin to the lumbosacral cord (23, 26). Its stimulation activates a network of lumbosacral neurons (30). In rats, the proerectile parasympathetic outflow originates in the sacral parasympathetic nucleus (SPN) of the L6-S1 spinal cord (28). The SPN contains the preganglionic neurons that innervate the penis (21). The neurotransmitters that activate the spinal proerectile network are presently unknown.The role of glutamate in the spinal control of the urinary and the lower digestive tracts has been established. In the rat, the NMDA gl...

Anatomical evidence for glutamatergic transmission in primary sensory neurons and onto postganglionic neurons controlling penile erection in rats: an ultrastructural study with neuronal tracing and immunocytochemistry

“…A network of lumbosacral neurons is excited by DPN stimulation in the anesthetized rat (Rampin et al 1997). D-2-amino-5-phosphonopentanoic acid or 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f)quinoxaline, NMDA, or AMPA glutamatergic receptor antagonists administered intrathecally block reflexive erections in conscious rats and depress the intracavernous pressure rise elicited by DPN stimulation in anesthetized rats (Rampin et al 2004). The present anatomical data reveal that at least the first step of this reflex loop, namely the primary afferents, contains a glutamatergic contingent.…”

“…Furthermore, GluR1 and GluR2 subunits of AMPA receptors are distributed in the superficial laminae of L5-L6 spinal segments at which penile afferents terminate, and GluR4 subunits are most intensively expressed in the MPG . Both AMPA and NMDA antagonists block reflexive erections in rats (Rampin et al 2004). As the pathways involved in reflexive erections are probably polysynaptic (Steers et al 1988), some if not all synapses of the reflex loop may therefore be glutamatergic: synapses between terminals of sensory afferents and their spinal target cells, and synapses between spinal interneurons and between interneurons and autonomic or somatic motoneurons.…”

Association Between Neuropathic Pain, Pregabalin Treatment, and Erectile Dysfunction

“…It is reported that, pregabalin decreases the release of neurotransmitters including glutamate, substance P and calcitonin gene‐related peptide [28]. In another study the authors concluded that glutamate, is a potent activator of the spinal proerectile network [29]. Also, substance p is a central neurotransmitter that facilitates sexual behavior [30].…”

Central nervous system-acting agents and the treatment of erectile and sexual dysfunction

“…CNS oxytocin transmission may mediate the action of both agents [38]. Direct or secondary oxytocin stimulation, therefore, may result in future CNS agents active in producing erectile function in men and facilitating sexual function in women.…”