title: 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.
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.
authors.affiliation: Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan, kzaitsu@med.nagoya-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Zaitsu
authors.forename: Izuru
authors.initials: I
authors.lastname: Miyawaki
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horie
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shima
authors.forename: Munehiro
authors.initials: M
authors.lastname: Katagi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Tatsuno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.forename: Takako
authors.initials: T
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuchihashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D008694:Methamphetamine / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D009294:Narcotics / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D019966:Substance-Related Disorders / Q000097:blood / Q000652:urine
chemical_list: D009294:Narcotics; D008694:Methamphetamine; D009020:Morphine; D003042:Cocaine