Dual pharmacological inhibitor of endocannabinoid degrading enzymes reduces depressive-like behavior in female rats

In this study we examined the role of endocannabinoids in depressive behavior. The levels of endocannabinoids, N-arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) were measured along with brain derived neurotrophic factor (BDNF) in postmortem ventral striata of female patients with MDD and non-psychiatric controls, and in Wistar Kyoto (WKY) rat, a selectively inbred strain of rat widely used for testing the depressive behavior. The effect of pharmacological elevation of endocannabinoids through inhibition of their catabolizing enzymes (fatty acid amide hydrolase [FAAH] and monoacyl glycerol lipase [MAGL]) on depressive-like phenotype was also assessed in WKY rat. The findings showed lower levels of endocannabinoids and BDNF in the ventral striatum of MDD patients and WKY rats. A dual inhibitor of FAAH and MAGL, JZL195, elevated the endocannabinods and BDNF levels in ventral striatum, and reduced the depressive-like phenotype in female WKY rats. Collectively, our study suggests a blunted endocannabinoid and BDNF signaling in ventral striatum of MDD/depressive behavior and concludes that endocannabinoid enhancing agents may have an antidepressant effect.
Source: Journal of Psychiatric Research - Category: Psychiatry Source Type: research