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Analytical and Bioanalytical Chemistry

, Volume 406, Issue 5, pp 1339–1354 | Cite as

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

  • Kei Zaitsu
  • Izuru Miyawaki
  • Kiyoko Bando
  • Hiroshi Horie
  • Noriaki Shima
  • Munehiro Katagi
  • Michiaki Tatsuno
  • Takeshi Bamba
  • Takako Sato
  • Akira Ishii
  • Hitoshi Tsuchihashi
  • Koichi Suzuki
  • Eiichiro Fukusaki
Research Paper

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.

Keywords

Metabolomics Drug addiction conditioned place preference Morphine Methamphetamine Cocaine 

Supplementary material

216_2013_7234_MOESM1_ESM.pdf (119 kb)
ESM 1 (PDF 118 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kei Zaitsu
    • 1
    • 2
  • Izuru Miyawaki
    • 3
  • Kiyoko Bando
    • 3
  • Hiroshi Horie
    • 3
  • Noriaki Shima
    • 2
  • Munehiro Katagi
    • 2
  • Michiaki Tatsuno
    • 2
  • Takeshi Bamba
    • 4
  • Takako Sato
    • 5
  • Akira Ishii
    • 1
  • Hitoshi Tsuchihashi
    • 5
  • Koichi Suzuki
    • 5
  • Eiichiro Fukusaki
    • 4
  1. 1.Department of Legal Medicine and BioethicsNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Forensic Science Laboratory, Osaka Prefectural Police HeadquartersOsakaJapan
  3. 3.Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, OsakaJapan
  4. 4.Department of Biotechnology, Graduate School of EngineeringOsaka UniversityOsakaJapan
  5. 5.Department of Legal Medicine, Osaka Medical CollegeTakatsuki CityJapan

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