Relationship between Cannabinoid CB1 and Dopamine D2 Receptors in Intestinal Motility in Mice

The possible presence of a functional interaction in the constipating effect of opioids and cannabinoids has been assessed. We have measured the ability of the opioid receptor antagonist, naloxone, to antagonize the inhibitory effect of the cannabinoid receptor agonist, WIN 55,212-2, and also, the ability of the cannabinoid CB1-receptor antagonist, SR 141716A, to antagonize the inhibitory effect of morphine, on transit of an orally administered, non-absorbable marker (carmine) in the mouse small intestine. Naloxone failed to alter the reducing effect of WIN 55,212-2 on the propulsive activity; conversely, pretreatment with SR 141716A did not prevent morphine-induced inhibition of marker transit. These results suggest that the constipating effect of opioids and cannabinoids occur through independent and unrelated mechanisms. We assessed also the possible existence of an interaction between CB1 and dopamine D2 receptor systems. The effect of the D2-receptor antagonist, S(-)-sulpiride, on the inhibiting effect of WIN 55,212-2 and of SR 141716A on the inhibiting effect of the D2 agonist, bromocriptine, on intestinal propulsion were assessed. Combination of 50 mg kg−1S(-)-sulpiride and 0.5 mg kg−1 WIN 55,212-2, but not higher doses, resulted in the blockade of WIN 55,212-2 effect; similarly, combination of 0.1 mg kg−1 SR 141716A abolished bromocriptine-induced decrease in intestinal motility. These results suggest the existence of a functional interaction between the CB1 and D2 receptors in mouse intestinal motility.