Bladder function in a cannabinoid receptor type 1 knockout mouse

Objective To evaluate bladder function in an established cannabinoid type 1 ( CB 1) receptor knockout ( KO ) mouse model via organ‐bath ( in vitro ) and urodynamic (cystometric; in vivo ) experiments.Materials and Methods In all, 20 8‐week‐old female wildtype ( WT ) mice ( C57BL /6) and 20 age‐matched CB 1 KO mice were used. Six mice from each group were used for the organ‐bath experiments, where the contractile responses of bladder tissue strips after carbachol exposure (carbachol concentration response curve [ CCRC ]; myogenic contraction) and during electrical field stimulation ( EFS ; neurogenic contraction) were assessed. In all, 14 mice per group were used for cystometric experiments without any anaesthesia, in which standard urodynamic variables were assessed 3 days after bladder catheterisation.Results The CCRCs of bladder strips from CB 1 KO mice were similar to those of WT mice. However, during EFS the bladder strips from the CB 1 KO mice had significantly lower contractile responses than WT preparations, indicating that in CB 1 KO mice the neuronal component of bladder contraction was different. In cystometric experiments the CB 1 KO mice had a higher micturition frequency (shorter mean [ sem ] inter‐micturition interval of 3.24 [0.29] vs 7.32 [0.5] min), a lower bladder capacity (0.09 [0.01] vs 0.18 [0.01] mL) and micturition volume (0.07 [0.01] vs 0.14 [0.01] mL), a lower bladder compliance (0.007 [0.001] vs 0.02 [0.002] mL/cmH 2 O), and higher spontaneous bladder activity (5.1 [0.5] vs 2.6 [0.6] cmH 2 O) than WT mice (all P < 0.05, S tudent's t ‐test). In WT mice, systemic administration of rimonabant ( SR 141716), a CB 1 receptor antagonist, resulted in urodynamic changes similar to those seen in the CB 1 KO mice.ConclusionsIn vitro , bladder strips from CB 1 KO mice responded to muscarinic receptor stimulation similarly as the WT controls, but were less responsive to electrical stimulation of nerves. In vivo , CB 1 KO mice had a higher micturition frequency and more spontaneous activity than WT mice. The present findings suggest that CB 1 receptors are involved in peripheral and central nervous control of micturition.