Investigation on the relationship between cannabinoid CB1and opioid receptors in gastrointestinal motility in mice

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Abstract
This study investigated whether (a) cannabinoid CB1receptor knockout (CB1−/−) mice displayed altered gastrointestinal transit and (b) cannabinoid CB1and opioid receptors functionally interact in the regulation of gastrointestinal transit. 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. 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. Additionally, in CD1 mice the cannabinoid CB1receptor 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. 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. British Journal of Pharmacology(2006)148, 1043–1050. doi:10.1038/sj.bjp.0706824