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Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference

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Abstract

The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography–MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid, l-tryptophan, cystine, and n-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction.

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Authors and Affiliations

  1. Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Kei Zaitsu & Akira Ishii

  2. Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka, 541-0053, Japan

    Kei Zaitsu, Noriaki Shima, Munehiro Katagi & Michiaki Tatsuno

  3. Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, 3-1-98 Kasugade-naka, Konohara-ku, , Osaka, 554-0022, Japan

    Izuru Miyawaki, Kiyoko Bando & Hiroshi Horie

  4. Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Takeshi Bamba & Eiichiro Fukusaki

  5. Department of Legal Medicine, Osaka Medical College, Daigakumachi 2-7, Takatsuki City, Osaka, 569-8686, Japan

    Takako Sato, Hitoshi Tsuchihashi & Koichi Suzuki

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  1. Kei Zaitsu
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  2. Izuru Miyawaki
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Correspondence to Kei Zaitsu.

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Published in the topical collection Biomedical Mass Spectrometry with guest editors Mitsutoshi Setou, Toshimitsu Niwa, and Akira Ishii.

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Zaitsu, K., Miyawaki, I., Bando, K. et al. Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference. Anal Bioanal Chem 406, 1339–1354 (2014). https://doi.org/10.1007/s00216-013-7234-1

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  • DOI: https://doi.org/10.1007/s00216-013-7234-1

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