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

Brain Res. 2004 Mar 5;999(2):227-30. doi: 10.1016/j.brainres.2003.12.004.

Abstract

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.

MeSH terms

  • Animals
  • Appetite Regulation / drug effects*
  • Appetite Regulation / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Brain / drug effects*
  • Brain / physiology
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoids / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Opioid Peptides / metabolism
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Receptor, Cannabinoid, CB1 / drug effects*
  • Receptor, Cannabinoid, CB1 / metabolism

Substances

  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Narcotic Antagonists
  • Opioid Peptides
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251
  • Naltrexone
  • nalmefene