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

1.The endocannabinoid system has been implicated in the control of gastrointestinal motility. The present study investigated whether (a) cannabinoid CB1 receptor knockout (CB1-/-) mice displayed an altered gastrointestinal transit when compared to homozygous CB1+/+ (CB1+/+) mice, and (b) the well-described functional interaction between the cannabinoid CB1 and opioid receptors extends to the regulation of gastrointestinal transit. 2.Gastrointestinal transit was assessed using two procedures: the Whole Gastrointestinal Transit, which measures the time to excretion of an intragastrically administered non-absorbable marker (whole intestine), and the Upper Gastrointestinal Transit, which measures the distance covered by the non-absorbable marker from pylorus to caecum (small intestine). 3.CB1-/- and CB1+/+ mice did not differ in basal levels of time of whole gut transit and distance travelled by the marker in the small intestine. CB1-/- and WT mice were equally responsive to the inhibitory effect of morphine (10 mg kg-1, i.p.) and loperamide (3 mg kg-1g, i.p.) on time of whole gut transit. 4.Additionally, in CD1 mice the cannabinoid CB1 receptor antagonist, rimonabant (SR 141716; 0-0.5 mg kg-1,i.p.),failed to block the inhibitory effect of morphine (0-1.25 mg kg-1g, i.p.) and loperamide (0-0.5 mg kg-1, i.p.) on transit in small and whole intestine. Similarly, the opioid receptor antagonists, naloxone (0-1 mg kg-1, i.p.) and naltrexone (0-10 mg kg-1, i.p.), failed to block the inhibitory effect of the cannabinoid WIN 55,212-2 (0-3 mg kg-1, i.p.) 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 on gastrointestinal motility; (b) cannabinoid and opioid receptor systems did not functionally interact in regulating gastrointestinal transit in mice.