5-HT3 receptors modulate changes in voiding pattern and bladder contractility in water avoidance stress-induced bladder overactivity in male mice

Published:October 03, 2022DOI:


      • Oral administration of 5-HT3 receptor antagonist, ondansetron, attenuates changes in urine voiding pattern in water avoidance stress-induced mice.
      • Enhanced spontaneous tonic and amplitude of contraction to cholinergic stimulation in the urinary bladder of stressed-mice was mediated via 5-HT3 receptors in the urinary bladder.
      • Mice exposed to repeated water avoidance stress showed less sensitivity to 5-HT-induced urinary bladder contraction.



      Chronic psychological stress aggravates painful bladder syndrome symptoms. Previous studies suggest roles of 5-HT3 receptors in regulating micturition and bladder hypersensitivity. This study aimed to investigate the roles of 5-HT3 receptors in modulating voiding patterns and spontaneous bladder contractile properties in water avoidance stress-induced mice.

      Materials and methods

      Voiding patterns in sham stress (SS), water avoidance stress (WS), and water avoidance stress with daily oral gavage of ondansetron (1 mg/kg BW) (WA) groups were analyzed after exposure to repeated water avoidance stress for 10 days. Changes in contractile activity of isolated bladder in response to KCl, carbachol, and 5-hydroxytryptamine were determined. Bladder mast cell quantification was examined using toluidine blue staining.


      Urine voided area was significantly decreased in WS group after exposure to 10 days of the stress protocol, which was reversed in the WA group. The WS group had a higher number of urine spots than the SS group. Increased mast cell degranulation was observed in the stressed mice. Bladder strips of the WS group showed higher tonic and amplitude of spontaneous contraction than the SS group, which were normalized by ondansetron administration. Increased response to carbachol-induced bladder contraction was observed in the bladder of stressed mice, which was attenuated with ondansetron pre-incubation.


      Water avoidance stress-induced mice exhibited changes in voiding pattern, which was reversed by oral administration with a 5-HT3 receptor antagonist (ondansetron). Enhanced contractile response to cholinergic stimulation in the urinary bladder of the psychological stress-induced bladder overactivity was mediated through 5-HT3 receptors.


      PBS (painful bladder syndrome), 5-HT (5-hydroxytryptamine), CCh (carbachol), SS (sham stress), WS (water avoidance stress), WA (water avoidance stress with oral administration of ondansetron)


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