A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice
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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.
KeywordsMonoacylglycerol lipase Social reward High-fat reward
The authors thank Terri Wang for her generous gift. The authors thank the Autism Science Foundation, the UC Irvine Center for Autism Research and Translation, and the UC Irvine Medical Scientist Training Program.
Compliance with ethical standards
All procedures met the National Institute of Health guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee at University of California, Irvine.
Conflict of interest
The authors declare that they have no competing interests.
- Brabant C, Quertemont E, Tirelli E (2005) Influence of the dose and the number of drug-context pairings on the magnitude and the long-lasting retention of cocaine-induced conditioned place preference in C57BL/6J mice. Psychopharmacology 180:33–40. doi: 10.1007/s00213-004-2138-6 CrossRefPubMedGoogle Scholar
- Kirkham TC, Williams CM, Fezza F, Marzo VD (2002) Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 136:550–557. doi: 10.1038/sj.bjp.0704767 CrossRefPubMedPubMedCentralGoogle Scholar
- Wei D, Lee D, Cox CD, et al. (2015) Endocannabinoid signaling mediates oxytocin-driven social reward. Proc Natl Acad Sci USA 201509795. doi: 10.1073/pnas.1509795112
- Williams CM, Kirkham TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptorsGoogle Scholar