Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice

Oral administration of the opioid antagonist nalmefene alone (up to 20 mg/kg) failed to show a significant effect on acute food intake in mice. However, combined oral dosing of nalmefene and subthreshold doses of AM251, a cannabinoid CB1 receptor inverse agonist, led to a significant reduction in fo...

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Bibliographic Details
Published in:Brain research 2004-03, Vol.999 (2), p.227-230
Main Authors: Chen, Richard Z., Huang, Ruey-Ruey C., Shen, Chun-Pyn, MacNeil, Douglas J., Fong, Tung M.
Format: Article
Language:English
Subjects:
AM251
Animals
Appetite Regulation - drug effects
Appetite Regulation - physiology
Biological and medical sciences
Body Weight - drug effects
Body Weight - physiology
Brain - drug effects
Brain - physiology
Cannabinoid
Cannabinoid Receptor Modulators - metabolism
Cannabinoids - pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Feeding. Feeding behavior
Food intake
Fundamental and applied biological sciences. Psychology
Homeostasis - drug effects
Homeostasis - physiology
Male
Mice
Mice, Inbred C57BL
Nalmefene
Naltrexone - analogs & derivatives
Naltrexone - pharmacology
Narcotic Antagonists - pharmacology
Obesity - metabolism
Obesity - physiopathology
Opioid
Opioid Peptides - metabolism
Piperidines - pharmacology
Pyrazoles - pharmacology
Receptor, Cannabinoid, CB1 - drug effects
Receptor, Cannabinoid, CB1 - metabolism
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Oral administration of the opioid antagonist nalmefene alone (up to 20 mg/kg) failed to show a significant effect on acute food intake in mice. However, combined oral dosing of nalmefene and subthreshold doses of AM251, a cannabinoid CB1 receptor inverse agonist, led to a significant reduction in food intake in both lean and diet-induced obese (DIO) mice. Furthermore, the anorectic effect of a high dose of AM251 was further enhanced when co-administered with nalmefene. The results support a synergistic interaction between opioid and cannabinoid systems in regulating feeding behavior.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2003.12.004