Role of the serotonergic system in urethral continence reflexes during sneezing in rats

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT_2C agonist) or LP44 (a 5-HT₇ agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH₂O and UBP by 13.3 cmH₂O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH₂O and UBP by 15.1 cmH₂O, and LP44 also increased A-URS by 20.6 cmH₂O and UBP by 11.4 cmH₂O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH₂O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH₂O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT_2C antagonist) and SB-269970 (a selective 5-HT₇ antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT_2C and 5-HT₇ receptors.