Bladder function in a cannabinoid receptor type 1 knockout mouse

Abstract

To evaluate bladder function in an established cannabinoid type 1 (CB1) receptor knockout (KO) mouse model via organ-bath (in vitro) and urodynamic (cystometric; in vivo) experiments. In all, 20 8-week-old female wildtype (WT) mice (C57BL/6) and 20 age-matched CB1 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. The CCRCs of bladder strips from CB1 KO mice were similar to those of WT mice. However, during EFS the bladder strips from the CB1 KO mice had significantly lower contractile responses than WT preparations, indicating that in CB1 KO mice the neuronal component of bladder contraction was different. In cystometric experiments the CB1 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/cmH2 O), and higher spontaneous bladder activity (5.1 [0.5] vs 2.6 [0.6] cmH2 O) than WT mice (all P < 0.05, Student's t-test). In WT mice, systemic administration of rimonabant (SR141716), a CB1 receptor antagonist, resulted in urodynamic changes similar to those seen in the CB1 KO mice. In vitro, bladder strips from CB1 KO mice responded to muscarinic receptor stimulation similarly as the WT controls, but were less responsive to electrical stimulation of nerves. In vivo, CB1 KO mice had a higher micturition frequency and more spontaneous activity than WT mice. The present findings suggest that CB1 receptors are involved in peripheral and central nervous control of micturition.