2-Arachidonoylglycerol as a possible treatment for anorexia nervosa in animal model in mice

Brain Res. 2017 Sep 1:1670:185-190. doi: 10.1016/j.brainres.2017.06.003. Epub 2017 Jun 9.


We have investigated the effects of 0.001mg/kg 2-arachidonoylglycerol (2-AG) administered in combination with compounds present in the body alongside 2-AG like 2-palmitoylglycerol and 2-linoleylglycerol (also termed "entourage"), on cognitive function,food intake, and neurotransmitter levels in the hippocampus and hypothalamus of mice under diet restriction. Young female Sabra mice were treated with vehicle, 2-AG, 2-AG+entourage, 2-AG+entourage+5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)- 4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR141716A, a CB1 antagonist) and SR141716A. The mice were fed for 2.5h a day for 14days. Cognitive function was evaluated by the eight arm maze test, and neurotransmitter (norepinephrine, dopamine, L-DOPA and serotonin) levels were measured in the hippocampus and hypothalamus by high-performance liquid chromatography-electrochemical detection. Food intake was increased by 2-AG and, to an even greater extent, by 2-AG+entourage. SR141716A reversed the effect of 2-AG+entourage. The administration of 2-AG+entourage improved cognitive function compared to the vehicle mice, and this improvement was blocked by SR141716A. 2-AG+entourage-treated mice showed an increase in norepinephrine (NE), dopamine and L-DOPA levels in the hippocampus. SR141716A normalized NE and L-DOPA levels. There were no significant changes in hypothalamic neurotransmitter levels. The use of very low doses of the endocannabinoid 2-AG+entourage can improve cognitive function by elevating norepinephrine and L-DOPA levels in the hippocampus, without cannabinomimetic side effects. These findings may have implications for cognitive enhancement in anorexia nervosa.

Keywords: 2-AG; Anorexia nervosa; Cognitive function; Entourage; Neurotransmitter levels; Regulation.

MeSH terms

  • Animals
  • Anorexia Nervosa / drug therapy*
  • Arachidonic Acids / pharmacology*
  • Cannabinoid Receptor Modulators / pharmacology
  • Cognition / drug effects
  • Disease Models, Animal
  • Dopamine / pharmacology
  • Eating / drug effects
  • Endocannabinoids / pharmacology*
  • Female
  • Glycerides / pharmacology*
  • Hippocampus / drug effects
  • Hypothalamus / drug effects
  • Levodopa / pharmacology
  • Mice
  • Neurotransmitter Agents / pharmacology
  • Random Allocation


  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Glycerides
  • Neurotransmitter Agents
  • 2-palmitoylglycerol
  • Levodopa
  • 2-linoleoylglycerol
  • glyceryl 2-arachidonate
  • Dopamine