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Publication : Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects.

First Author  Zhang J Year  2024
Journal  iScience Volume  27
Issue  2 Pages  108919
PubMed ID  38318362 Mgi Jnum  J:351259
Mgi Id  MGI:7581669 Doi  10.1016/j.isci.2024.108919
Citation  Zhang J, et al. (2024) Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects. iScience 27(2):108919
abstractText  Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.
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