2-Arachidonoylglycerol as a possible treatment for anorexia nervosa in animal model in mice.
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.
['Avraham|Y|Y|', 'Paturski|I|I|', 'Magen|I|I|', 'Vorobiev|L|L|', 'Berry|E M|EM|']
D000818:Animals D000856:Anorexia Nervosa D001095:Arachidonic Acids D063385:Cannabinoid Receptor Modulators D003071:Cognition D004195:Disease Models, Animal D004298:Dopamine D004435:Eating D063388:Endocannabinoids D005260:Female D005989:Glycerides D006624:Hippocampus D007031:Hypothalamus D007980:Levodopa D051379:Mice D018377:Neurotransmitter Agents D011897:Random Allocation
Anorexia nervosa 2-AG Entourage Cognitive function Neurotransmitter levels Regulation