title: Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.
abstract: Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.
authors: Department of Molecular Medicine, University of Padova, Padova, Italy; National Institute of Biostructures and Biosystems, Roma, Italy.
authors: Marco
authors: M
authors: Redaelli
authors: Department of Molecular Medicine, University of Padova, Padova, Italy; Cell Biology and Neuroscience Institute, University of Buenos Aires-National Scientific and Technical Council (UBA-CONICET), Buenos Aires, Argentina.
authors: María Jimena
authors: MJ
authors: Ricatti
authors: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors: Marialaura
authors: M
authors: Simonetto
authors: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors: Mirko
authors: M
authors: Claus
authors: Ronzoni-Villa Foundation, Seregno, Italy.
authors: Maurizio
authors: M
authors: Ballabio
authors: National Institute of Biostructures and Biosystems, Roma, Italy; Pharmaceutical Department, University of Parma, Parma, Italy.
authors: Antonio
authors: A
authors: Caretta
authors: Department of Molecular Medicine, University of Padova, Padova, Italy; National Institute of Biostructures and Biosystems, Roma, Italy.
authors: Carla
authors: C
authors: Mucignat-Caretta
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D051379:Mice; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects; D014554:Urination / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D003520:Cyclophosphamide