Canna~Fangled Abstracts

Genetic Disruption of 2-Arachidonoylglycerol Synthesis Reveals a Key Role for Endocannabinoid Signaling in Anxiety Modulation.

By November 26, 2014 No Comments
2014 Nov 26. pii: S2211-1247(14)00955-3. doi: 10.1016/j.celrep.2014.11.001. [Epub ahead of print]

pm1Genetic Disruption of 2-Arachidonoylglycerol Synthesis Reveals a Key Role for Endocannabinoid Signaling in Anxiety Modulation.


Endocannabinoid (eCB) signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG) in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα) in mice reduces brain, but not circulating, 2-AG levels. DAGLα deletion also results in anxiety-like and sex-specific anhedonic phenotypes associated with impaired activity-dependent eCB retrograde signaling at amygdala glutamatergic synapses. Importantly, acute pharmacological normalization of 2-AG levels reverses both phenotypes of DAGLα-deficient mice. These data suggest 2-AG deficiency could contribute to the pathogenesis of affective disorders and that pharmacological normalization of 2-AG signaling could represent an approach for the treatment of mood and anxiety disorders.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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  • DAGLα deletion reduces CNS, but not circulating, 2-AG levels
  • DAGLα knockout mice exhibit anxiety and sex-specific depressive behaviors
  • DAGLα deletion impairs endocannabinoid suppression of amygdala glutamate release
  • Normalizing 2-AG levels reverses the behavioral phenotype of DAGLα-deficient mice


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