Effects of the CB1 cannabinoid receptor inverse agonist AM251 on food intake and body weight in mice lacking μ-opioid receptors

Abstract We used μ-opioid receptor-deficient (MOR−/−) mice to determine the effects of the CB1 cannabinoid receptor inverse agonist AM251 on feeding in the absence of MOR signaling. A single dose of AM251 at 0.6, 2 or 6 mg/kg caused similar dose-dependent suppression of food intake in wild-type and MOR−/− mice. Administration of AM251 at 3 mg/kg/day for 9 consecutive days also led to a similar reduction (∼8%) in body weight in wild-type and MOR−/− mice. Our results suggest that MOR signaling is not necessary for cannabinoid-mediated effects on feeding and that physiological antagonism of opioid receptor tone might be required for the observed synergistic effects of a CB1 inverse agonist and an opioid receptor antagonist on feeding.