Journal
NEUROPHARMACOLOGY
Volume 124, Issue -, Pages 38-51Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2017.05.033
Keywords
Endocannabinoids; Hypothalamus; VTA; NAc; PFC; Food intake; Obesity; Synaptic transmission
Categories
Funding
- Club Foundation [FDN 148473]
- Alberta Innovates Health Solutions postdoctoral fellowship
- Region Aquitaine
- Institut national de la sante et de la recherche medicale (INSERM)
- Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens) [ANR-13-BSV4-0006]
- Fondation Francophone pour la Recherche sur le Diabete - Federation Francaise des Diabetiques (AFD)
- AstraZeneca
- Eli Lilly
- Merck Sharp Dohme
- Novo Nordisk
- Sanofi
- Endocannabinoid Research Group at the Institute of Biomolecular Chemistry of CNR
- Alberta Innovates [201500690] Funding Source: researchfish
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The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesting that endocannabinoids may act in the hypothalamus to integrate different types of signals informing about the animal's energy needs. In the mesocorticolimbic system, (endo)cannabinoids modulate synaptic transmission to promote dopamine release in response to palatable food. In addition, (endo)cannabinoids act within the nucleus accumbens to increase food's hedonic impact; although this effect depends on activation of CB1Rs at excitatory, but not inhibitory inputs in the nucleus accumbens. While hyperactivation of the endocannabinoid system is typically associated with overeating and obesity, much evidence has emerged in recent years suggesting a more complicated system than first thought endocannabinoids promote or suppress feeding depending on cell and input type, or modulation by various neuronal or hormonal signals. This review presents our latest knowledge of the endocannabinoid system in non-homeostatic and homeostatic feeding circuits. In particular, we discuss the functional role and cellular mechanism of action by endocannabinoids within the hypothalamus and mesocorticolimbic system, and how these are modulated by neuropeptide signals related to feeding. In light of recent advances and complexity in the field, we review cannabinoid-based therapeutic strategies for the treatment of obesity and how peripheral restriction of CB1R antagonists may provide a different mechanism of weight loss without the central adverse effects. This article is part of the Special Issue entitled A New Dawn in Cannabinoid Neurobiology. (C) 2017 Elsevier Ltd. All rights reserved.
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