Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects
Jinming Zhang,
Junmin Zhang,
Ruiqi Yuan,
Wenxin Han,
Yuan Chang,
Lingyang Kong,
Chunling Wei,
Qiaohua Zheng,
Xingchao Zhu,
Zhiqiang Liu,
Wei Ren,
Jing Han
Affiliations
Jinming Zhang
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Junmin Zhang
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Ruiqi Yuan
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Wenxin Han
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Yuan Chang
Department of Histology and Embryology, School of Basic Medical Science, Xi’an Medical University, Xi’an 710000, China
Lingyang Kong
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Chunling Wei
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Qiaohua Zheng
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Xingchao Zhu
Heze Hospital of Traditional Chinese Medicine, Heze 274000, China
Zhiqiang Liu
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China
Wei Ren
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China; Faculty of Education, Shaanxi Normal University, Xi’an 710000, China
Jing Han
Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi’an 710000, China; Corresponding author
Summary: 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.
