PMID- 31270353
OWN - NLM
STAT- MEDLINE
DCOM- 20201026
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Jul 3
TI  - Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: 
      mechanism and effect on learning and memory.
PG  - 9621
LID - 10.1038/s41598-019-45969-4 [doi]
LID - 9621
AB  - 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.
FAU - Li, Ren-Shi
AU  - Li RS
AD  - Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan.
AD  - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 
      211198, People's Republic of China.
FAU - Fukumori, Ryo
AU  - Fukumori R
AD  - Department of Pharmacotherapeutics and Neuropsychopharmacology, Faculty of 
      Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, 
      Japan.
FAU - Takeda, Tomoki
AU  - Takeda T
AD  - Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan.
FAU - Song, Yingxia
AU  - Song Y
AD  - Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan.
FAU - Morimoto, Satoshi
AU  - Morimoto S
AD  - Division of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu 
      University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
FAU - Kikura-Hanajiri, Ruri
AU  - Kikura-Hanajiri R
AD  - Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of 
      Health Sciences (NIHS), 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-city, Kanagawa, 
      210-9501, Japan.
FAU - Yamaguchi, Taku
AU  - Yamaguchi T
AD  - Department of Pharmacotherapeutics and Neuropsychopharmacology, Faculty of 
      Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, 
      Japan.
FAU - Watanabe, Kazuhito
AU  - Watanabe K
AD  - Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku Fukuoka, 815-8511, 
      Japan.
FAU - Aritake, Kousuke
AU  - Aritake K
AD  - Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku Fukuoka, 815-8511, 
      Japan.
FAU - Tanaka, Yoshitaka
AU  - Tanaka Y
AD  - Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan.
FAU - Yamada, Hideyuki
AU  - Yamada H
AD  - Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan.
FAU - Yamamoto, Tsuneyuki
AU  - Yamamoto T
AD  - Department of Pharmacotherapeutics and Neuropsychopharmacology, Faculty of 
      Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, 
      Japan.
FAU - Ishii, Yuji
AU  - Ishii Y
AUID- ORCID: 0000-0002-2069-0219
AD  - Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, 
      Japan. ishii@phar.kyushu-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190703
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cannabinoids)
RN  - 0 (Endocannabinoids)
RN  - 0 (Indoles)
RN  - 0 (Naphthalenes)
RN  - G391998J57 (1-pentyl-3-(1-naphthoyl)indole)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Brain/*drug effects/*physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cannabinoids/adverse effects/chemistry/*pharmacology
MH  - Endocannabinoids/*biosynthesis
MH  - Hippocampus/metabolism
MH  - Indoles/adverse effects/chemistry/*pharmacology
MH  - Learning/drug effects
MH  - Memory/drug effects
MH  - Metabolome
MH  - Metabolomics/methods
MH  - Mice
MH  - Naphthalenes/adverse effects/chemistry/*pharmacology
MH  - Spectrum Analysis
PMC - PMC6610139
COIS- The authors declare no competing interests.
EDAT- 2019/07/05 06:00
MHDA- 2020/10/27 06:00
PMCR- 2019/07/03
CRDT- 2019/07/05 06:00
PHST- 2019/03/22 00:00 [received]
PHST- 2019/06/19 00:00 [accepted]
PHST- 2019/07/05 06:00 [entrez]
PHST- 2019/07/05 06:00 [pubmed]
PHST- 2020/10/27 06:00 [medline]
PHST- 2019/07/03 00:00 [pmc-release]
AID - 10.1038/s41598-019-45969-4 [pii]
AID - 45969 [pii]
AID - 10.1038/s41598-019-45969-4 [doi]
PST - epublish
SO  - Sci Rep. 2019 Jul 3;9(1):9621. doi: 10.1038/s41598-019-45969-4.