Effects of the CB1 cannabinoid receptor inverse agonist AM251 on food intake and body weight in mice lacking mu-opioid receptors.
We used mu-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 ( approximately 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.
Chen
Richard Z
RZ
Department of Metabolic Disorders, Merck Research Laboratories, P.O. Box 2000, RY80M-213, Rahway, NJ 07065, USA. richard_z_chen@merck.com
Frassetto
Andrea
A
Fong
Tung M
TM
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout; D018847:Opioid Peptides / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics*
D063385:Cannabinoid Receptor Modulators; D018847:Opioid Peptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017450:Receptors, Opioid, mu; C103505:AM 251