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Miyazato M, Kaiho Y, Kamo I, Kitta T, Chancellor MB, Sugaya K, Arai Y, de Groat WC, Yoshimura N: Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol. 2009 Oct;297(4):F1024-31. Epub 2009 Jul 29.
To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT (1A) agonist), mCPP (a 5-HT (2B/2C) agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT (1A) antagonist, and RS-102221 (it), a selective 5-HT (2C) antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT (2C) receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT (1A) inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT (2C) receptors and inhibitory 5-HT receptors other than the 5-HT (1A) subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT (2C) could be effective for the treatment of SUI. |
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