OBJECTIVE:

To evaluate bladder function in an established cannabinoid type 1 (CB1) receptor knock-out mouse model via organ bath (in vitro) and urodynamic (cystometric; in vivo) experiments.

MATERIALS & METHODS:

Twenty 8-week-old female wildtype (WT) mice (C57BL/6) and 20 age-matched CB1 knock-out (KO) mice were used. Six animals of each group were used for organ bath experiments where the contractile responses of bladder tissue strips following carbachol exposure (CCRC, carbachol concentration response curve) (myogenic contraction) and during electrical field stimulation (EFS) (neurogenic contraction) were assessed. Fourteen animals per group were used for cystometric experiments without any anesthesia, in which standard urodynamic parameters were assessed three days following bladder catheterization.

RESULTS:

The CCRC of bladder strips from CB1 KO mice was similar to that of WT animals. However, during EFS the bladder strips from CB1 KO mice had a significantly lower contractile response than WT preparations, indicating that in CB1 KO animals the neuronal component of bladder contraction was different. In cystometric experiments CB1 KO mice showed a higher micturition frequency (shorter inter-micturition interval: 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 a higher spontaneous bladder activity (5.1 ±0.5 vs. 2.6 ±0.6 cmH₂ O) than WT mice (all p < 0.05 using Student’s t-test). In WT animals, systemic administration of rimonabant (SR141716), a CB1 receptor antagonist, resulted in urodynamic changes similar to those in CB1 KO mice.

CONCLUSIONS:

In vitro, bladder strips from CB1 KO mice responded to muscarinic receptor stimulation similar to 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 animals. The present findings suggest that CB1 receptors are involved in peripheral and central nervous control of micturition.
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PMID:

 

24053792

 

[PubMed – as supplied by publisher]