Brain serotoninergic nervous system is involved in bombesin‐induced frequent urination through brain 5‐HT 7 receptors in rats

Background and Purpose Psychological stress exacerbates symptoms of urinary bladder dysfunction; however, the underlying brain mechanisms are unclear. We have demonstrated that centrally administered bombesin, a stress‐related neuropeptide, facilitates the rat micturition reflex. Brain bombesin‐like peptides modulate the serotoninergic nervous system activity under stress conditions; therefore, we examined whether brain 5‐HT is involved in the bombesin‐induced increased frequency of urination in urethane‐anaesthetised male Sprague–Dawley rats. Experimental Approach Evaluation of intercontraction intervals (ICI) and maximal voiding pressure (MVP) during cystometrograms were started 1 h before i.c.v. administration of bombesin or i.c.v. pretreatment with the 5‐HT receptor antagonists. Key Results Bombesin (0.03 nmol per animal, i.c.v.) significantly reduced ICI without affecting MVP. The bombesin‐induced response was significantly suppressed by acute depletion of brain 5‐HT, which was induced by pretreatment with p ‐chlorophenylalanine, a 5‐HT synthesis inhibitor. Bombesin at a lower dose (0.01 nmol per animal, i.c.v.) showed no significant effect on ICI, while it significantly reduced ICI in the presence of WAY‐100635 (5‐HT 1A receptor antagonist, 0.1 or 0.3 μg per animal, i.c.v.), which can block the negative feedback control of 5‐HT release. Bombesin (0.03 nmol per animal)‐induced ICI reduction was significantly attenuated by SB269970 (5‐HT 7 receptor antagonist, 0.1 or 0.3 μg per animal, i.c.v.) but not by ritanserin (5‐HT 2 receptor antagonist, 0.3 or 1 μg per animal, i.c.v.). Conclusions and Implications The brain serotoninergic nervous system is involved in the facilitation of the rat micturition reflex induced by bombesin‐like peptides at least in part through brain 5‐HT 7 receptors.