Metabolome disruption of the rat cerebrum induced by the acute toxic effects of the synthetic cannabinoid MAM-2201

Aim: The aim of this study is to investigate the metabolome disruption in the rat cerebrum induced by the recently abused synthetic cannabinoid MAM-2201. Main methods: MAM-2201 was intraperitoneally administered to 6-week Wistar rats at 5 or 15 mg/kg (n = 5), and the cerebrum metabolome alteration was investigated using a gas chromatography/tandem mass spectrometry (GC/MS/MS)-based metabolomics technique. Key findings: MAM-2201 induced oligopnea and hypokinesia at the 5 mg/kg dose, while more abnormal symptoms like rotational and seizure-like behaviors were observed at the 15 mg/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. Significance: 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. (C) 2015 Elsevier Inc. All rights reserved.