Characterization of bladder function in a cannabinoid receptor type 2 knockout mouse in vivo and in vitro

Aims The contribution of individual CB receptors (CB1R and CB2R) to normal micturition has not been clearly defined. Our goal was to study if differences in urodynamic parameters or in vitro bladder contractility can be demonstrated between CB2R knockout (CB2RKO) and C57BL/6J control (wild type, WT) mice. Methods Female WT and CB2RKO mice underwent bladder catheterization and cystometry was performed after 2 and 3 days. Cystometric evaluations were performed in awake animals without drug administration, and WT were also given HU-308 (CB2R agonist) followed by AM630 (CB2R antagonist). Bladders were removed for in vitro assessment of contractile responses to carbachol and electrical field stimulation (EFS). Results CB2RKO mice had significantly higher intercontraction intervals (ICIs), bladder capacity (BC) and compliance (Bcom) than WT controls (P<0.05). In WT mice, BC and ICI were increased from baseline by HU-308 exposure, and then returned to baseline levels after AM630 administration (P<0.05). There were no differences in contractility after carbachol or EFS between the groups. Conclusions Lack of CB2R was associated with longer ICI and higher BC and Bcom than its presence (WT controls). This was unexpected since in WT, an increase in BC and ICI from baseline was observed after CB2R agonist administration, and this action was reversed by a CB2R antagonist. Since there were no differences in the in vitro responses to carbachol and EFS in bladder strips, it may be speculated that the urodynamic differences are caused by a change in the central nervous micturition control in CB2RKO animals. Neurourol. Urodynam. 33:566-570, 2014. (c) 2013 Wiley Periodicals, Inc.