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

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

Author information

1
Department of Human Nutrition and Metabolism Hebrew University - Hadassah Medical School, POB 12272, Jerusalem 91120, Israel. Electronic address: yosefa@md.huji.ac.il.
2
Department of Human Nutrition and Metabolism Hebrew University - Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.

Abstract

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

PMID:
28606779
DOI:
10.1016/j.brainres.2017.06.003
[Indexed for MEDLINE]

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