| First Author | Hermanson DJ | Year | 2013 |
| Journal | Nat Neurosci | Volume | 16 |
| Issue | 9 | Pages | 1291-8 |
| PubMed ID | 23912944 | Mgi Jnum | J:203884 |
| Mgi Id | MGI:5528961 | Doi | 10.1038/nn.3480 |
| Citation | Hermanson DJ, et al. (2013) Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat Neurosci 16(9):1291-8 |
| abstractText | Augmentation of endogenous cannabinoid (eCB) signaling represents an emerging approach to the treatment of affective disorders. Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid to form prostaglandins, but also inactivates eCBs in vitro. However, the viability of COX-2 as a therapeutic target for in vivo eCB augmentation has not been explored. Using medicinal chemistry and in vivo analytical and behavioral pharmacological approaches, we found that COX-2 is important for the regulation of eCB levels in vivo. We used a pharmacological strategy involving substrate-selective inhibition of COX-2 to augment eCB signaling without affecting related non-eCB lipids or prostaglandin synthesis. Behaviorally, substrate-selective inhibition of COX-2 reduced anxiety-like behaviors in mice via increased eCB signaling. Our data suggest a key role for COX-2 in the regulation of eCB signaling and indicate that substrate-selective pharmacology represents a viable approach for eCB augmentation with broad therapeutic potential. |
