title: Metabolome disruption of the rat cerebrum induced by the acute toxic effects of the synthetic cannabinoid MAM-2201.
abstract: OBJECTIVE
  The aim of this study is to investigate the metabolome disruption in the rat cerebrum induced by the recently abused synthetic cannabinoid MAM-2201.
  
  
  METHODS
  MAM-2201 was intraperitoneally administered to 6-week Wistar rats at 5 or 15mg/kg (n=5), and the cerebrum metabolome alteration was investigated using a gas chromatography/tandem mass spectrometry (GC/MS/MS)-based metabolomics technique.
  
  
  RESULTS
  MAM-2201 induced oligopnea and hypokinesia at the 5mg/kg dose, while more abnormal symptoms like rotational and seizure-like behaviors were observed at the 15mg/kg dose, suggesting that MAM-2201 induced neurofunctional disruptions. GC/MS/MS detected 72 metabolites in the rat cerebrum. The cerebrum levels of 12 of these metabolites, including intermediates of the tricarboxylic acid cycle (malic acid and succinic acid) and glutamic acid (Glu), were significantly changed in MAM-2201 administered groups compared to the control group.
  
  
  CONCLUSIONS
  The synthetic cannabinoid MAM-2201 can disrupt not only glutamatergic neurotransmission but also energy metabolism in the rat cerebrum. Such disruption may contribute to the abnormal symptoms induced by synthetic cannabinoids.
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Electronic address: kzaitsu@med.nagoya-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Zaitsu
authors.affiliation: Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Nanpei
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Takahara
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kusano
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Legal Medicine, Osaka Medical College, Daigakumachi 2-7, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuchihashi
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000633:toxicity; D054022:Cerebrum / Q000187:drug effects* / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000139:chemically induced; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D018476:Hypokinesia / Q000139:chemically induced; D007211:Indoles / Q000633:toxicity*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D009281:Naphthalenes / Q000633:toxicity*; D051381:Rats; D012640:Seizures / Q000139:chemically induced
chemical_list: C000594853:1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole; D002186:Cannabinoids; D007211:Indoles; D009281:Naphthalenes; D018698:Glutamic Acid
keywords: Cerebrum; Energy metabolism disruption; MAM-2201; Metabolomics; Synthetic cannabinoid