Activity-based anorexia in C57/BL6 mice: effects of the phytocannabinoid, Delta9-tetrahydrocannabinol (THC) and the anandamide analogue, OMDM-2

Eur Neuropsychopharmacol. 2010 Sep;20(9):622-31. doi: 10.1016/j.euroneuro.2010.04.002. Epub 2010 May 14.

Abstract

The activity-based anorexia (ABA) paradigm is one of the few animal models of human anorexia nervosa. We present here the translation of this approach to C57/BL6 mice, a common background for genetically modified mice, and investigate the effects of the cannabinoid agonist, Delta(9)-tetrahydrocannabinol (THC) and the endocannabinoid uptake inhibitor, OMDM-2 in this model. The ABA paradigm was optimised so that food-restricted wheel-running mice displayed anorexia, reduced body weight and disrupted activity and circadian cycles. These conditions produced a murine ABA model with a defined stage and stability to allow for pharmacological intervention. Daily Delta(9)-THC (0.5 mg/kg) decreased survival in the ABA animals but increased feeding in the survivors, OMDM-2 (3 mg/kg) increased food intake, but not sufficiently to reverse weight loss. The effects of this model on endocannabinoid tone in the brain remain to be determined. Since the endocannabinoid system may be implicated in anorexia nervosa and in view of the positive modulation by cannabinoids of some aspects of ABA in this study, further investigation of the effects of cannabinoids in ABA is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia Nervosa / drug therapy*
  • Anorexia Nervosa / metabolism
  • Anorexia Nervosa / physiopathology*
  • Arachidonic Acids / pharmacology*
  • Arachidonic Acids / toxicity
  • Benzyl Compounds / pharmacology*
  • Benzyl Compounds / toxicity
  • Disease Models, Animal
  • Dronabinol / pharmacology*
  • Dronabinol / toxicity
  • Energy Intake / drug effects
  • Energy Metabolism / drug effects
  • Feeding Behavior
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Physical Conditioning, Animal
  • Psychotropic Drugs / pharmacology*
  • Psychotropic Drugs / toxicity
  • Weight Loss

Substances

  • Arachidonic Acids
  • Benzyl Compounds
  • OMDM-2 cpd
  • Psychotropic Drugs
  • Dronabinol