Investigation on the relationship between cannabinoid CB1 and opioid receptors in gastrointestinal motility in mice

1 This study investigated whether (a) cannabinoid CB1 receptor knockout (CB1-/-) mice displayed altered gastrointestinal transit and (b) cannabinoid CB1 and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2 Gastrointestinal transit was assessed by the Whole Gastrointestinal Transit, measuring the excretion time of an intragastrically administered marker ( whole intestine), and the Upper Gastrointestinal Transit, measuring the distance covered by the marker in the small intestine. 3 CB1-/- and homozygous CB1-/- (CB1-/-) mice did not differ in both whole gut and small intestine transit. CB1-/- and CB1-/- mice were equally responsive to the inhibitory effect of morphine (10 mg kg(-1)) and loperamide (3 mg kg(-1)) on whole gut transit. 4 Additionally, in CD1 mice the cannabinoid CB1 receptor antagonist, rimonabant (0-0.5 mg kg(-1)), failed to block the inhibitory effect of morphine (0-1.25 mg kg(-1)) and loperamide (0-0.5 mg kg(-1)) on transit in small and whole intestine. Similarly, the opioid receptor antagonists, naloxone (0-1 mg kg(-1)) and naltrexone ( 0 - 10 mg kg(-1)), failed to block the inhibitory effect of the cannabinoid WIN 55,212-2 (0-3 mg kg(-1)) on transit in small and whole intestine. 5 These results suggest that (a) compensatory mechanisms likely developed in CB1-/- mice to overcome the lack of inhibitory function of endocannabinoid system; (b) cannabinoid and opioid receptor systems did not interact in regulating gastrointestinal transit in mice.