Roles of the spinal glutamatergic pathway activated through α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence mechanisms

Aims: To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats. Methods: In female Sprague-Dawley rats under urethane anesthesia, the effects of an α-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]_2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated. Results: Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT_2B/2C, agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.). Conclusion: These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats.