Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory

Ren Shi Li, Ryo Fukumori, Tomoki Takeda, Yingxia Song, Satoshi Morimoto, Ruri Kikura-Hanajiri, Taku Yamaguchi, Kazuhito Watanabe, Kousuke Aritake, Yoshitaka Tanaka, Hideyuki Yamada, Tsuneyuki Yamamoto, Yuji Ishii

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

The impairment of learning and memory is a well-documented effect of both natural and synthetic cannabinoids. In the present study, we aimed to investigate the effect of acute administration of JWH-018, a synthetic cannabinoid, on the hippocampal metabolome to assess biochemical changes in vivo. JWH-018 elevated levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The increase of endocannabinoid levels in response to JWH-018 could be inhibited by co-administration of AM251, a CB1 receptor antagonist. Biochemical analyses revealed that this was the result of suppression of two hydrolases involved in endocannabinoid degradation (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL]). Additionally, we showed that JWH-018 causes a reduction in the levels of brain-derived neurotrophic factor (BDNF), which is known to modulate synaptic plasticity and adaptive processes underlying learning and memory. The decrease of BDNF following JWH-018 treatment was also rescued by co-administration of AM251. As both endocannabinoids and BDNF have been shown to modulate learning and memory in the hippocampus, the alteration of their levels in response to JWH-018 may explain the contribution of synthetic cannabinoids to impairment of memory.

本文言語英語
論文番号9621
ページ数1
ジャーナルScientific reports
9
1
DOI
出版ステータス出版済み - 7月 3 2019

!!!All Science Journal Classification (ASJC) codes

  • 一般

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