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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F1024    most recent 00297.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Miyazato, M. Articles by Yoshimura, N. PubMed PubMed Citation Articles by Miyazato, M. Articles by Yoshimura, N.

Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats

Departments of ¹ Urology and ; ²Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; ; ³Department of Urology, William Beaumont Hospital, Royal Oak, Michigan; ; ⁴Division of Urology, Department of Organ-Oriented Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa; and ; ⁵Department of Urology, Tohoku University School of Medicine, Miyagi, Japan

Submitted May 29, 2009 ; accepted in final form July 23, 2009

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.

urinary incontinence; neural pathway; serotonergic reuptake inhibitors; birth trauma