| First Author | Shonesy BC | Year | 2014 |
| Journal | Cell Rep | Volume | 9 |
| Issue | 5 | Pages | 1644-53 |
| PubMed ID | 25466252 | Mgi Jnum | J:222187 |
| Mgi Id | MGI:5644104 | Doi | 10.1016/j.celrep.2014.11.001 |
| Citation | Shonesy BC, et al. (2014) Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation. Cell Rep 9(5):1644-53 |
| abstractText | 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 alpha (DAGLalpha) in mice reduces brain, but not circulating, 2-AG levels. DAGLalpha 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 DAGLalpha-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. |
