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記事

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.

元の言語英語
ページ数1
ジャーナルScientific reports
9
発行部数1
DOI
出版物ステータス出版済み - 7 3 2019

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Endocannabinoids
Cannabinoids
Learning
Brain-Derived Neurotrophic Factor
Brain
Monoacylglycerol Lipases
Cannabinoid Receptor CB1
Neuronal Plasticity
Metabolome
Hydrolases
1-pentyl-3-(1-naphthoyl)indole
Hippocampus

All Science Journal Classification (ASJC) codes

  • General

これを引用

Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018 : mechanism and effect on learning and memory. / Li, Ren Shi; Fukumori, Ryo; Takeda, Tomoki; Song, Yingxia; Morimoto, Satoshi; Kikura-Hanajiri, Ruri; Yamaguchi, Taku; Watanabe, Kazuhito; Aritake, Kousuke; Tanaka, Yoshitaka; Yamada, Hideyuki; Yamamoto, Tsuneyuki; Ishii, Yuji.

:: Scientific reports, 巻 9, 番号 1, 03.07.2019.

研究成果: ジャーナルへの寄稿記事

Li, RS, Fukumori, R, Takeda, T, Song, Y, Morimoto, S, Kikura-Hanajiri, R, Yamaguchi, T, Watanabe, K, Aritake, K, Tanaka, Y, Yamada, H, Yamamoto, T & Ishii, Y 2019, 'Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory', Scientific reports, 巻. 9, 番号 1. https://doi.org/10.1038/s41598-019-45969-4
Li, Ren Shi ; Fukumori, Ryo ; Takeda, Tomoki ; Song, Yingxia ; Morimoto, Satoshi ; Kikura-Hanajiri, Ruri ; Yamaguchi, Taku ; Watanabe, Kazuhito ; Aritake, Kousuke ; Tanaka, Yoshitaka ; Yamada, Hideyuki ; Yamamoto, Tsuneyuki ; Ishii, Yuji. / Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018 : mechanism and effect on learning and memory. :: Scientific reports. 2019 ; 巻 9, 番号 1.
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abstract = "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.",
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