A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice
Psychopharmacology, 2016•Springer
Rationale The endocannabinoid system is an important modulator of brain reward signaling.
Investigations have focused on cannabinoid (CB 1) 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 …
Investigations have focused on cannabinoid (CB 1) 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 …
Rationale
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.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
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