title: A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice.
abstract: The endocannabinoid system is an important modulator of brain reward signaling. Investigations have focused on cannabinoid (CB1) receptors, because dissection of specific contributions of individual endocannabinoids has been limited by the available toolset. While we recently described an important role for the endocannabinoid anandamide in the regulation of social reward, it remains to be determined whether the other major endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), serves a similar or different function.
  
  
  
  To study the role of 2-AG in natural reward, we used a transgenic mouse model (MGL-Tg mice) in which forebrain 2-AG levels are selectively reduced. We complemented behavioral analysis with measurements of brain 2-AG levels.
  
  
  
  We tested male MGL-Tg mice in conditioned place preference (CPP) tasks for high-fat food, social contact, and cocaine. We measured 2-AG content in the brain regions of interest by liquid chromatography/mass spectrometry.
  
  
  
  Male MGL-Tg mice are impaired in developing CPP for high-fat food and social interaction, but do develop CPP for cocaine. Furthermore, compared to isolated mice, levels of 2-AG in socially stimulated wild-type mice are higher in the nucleus accumbens and ventral hippocampus (183 and 140 % of controls, respectively), but unchanged in the medial prefrontal cortex.
  
  
  
  The results suggest that reducing 2-AG-mediated endocannabinoid signaling impairs social and high-fat food reward in male mice, and that social stimulation mobilizes 2-AG in key brain regions implicated in the control of motivated behavior. The time course of this response differentiates 2-AG from anandamide, whose role in mediating social reward was previously documented.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA.
authors.forename: Don
authors.identifier: 0000-0003-2198-5921
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA.
authors.forename: DaYeon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA.|Department of Ophthalmology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Daglian
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA.
authors.forename: Kwang-Mook
authors.initials: KM
authors.lastname: Jung
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697, USA. piomelli@uci.edu.|Unit of Drug Discovery and Development, Italian Institute of Technology, Genova, Italy. piomelli@uci.edu.|Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA. piomelli@uci.edu.
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D003213:Conditioning, Psychological; D004041:Dietary Fats / Q000008:administration & dosage; D063388:Endocannabinoids / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D011897:Random Allocation; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction; D012919:Social Behavior
chemical_list: D004041:Dietary Fats; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D008994:Monoacylglycerol Lipases; D003042:Cocaine
keywords: High-fat reward; Monoacylglycerol lipase; Social reward