title: ¹H NMR-based metabonomic analysis of brain in rats of morphine dependence and withdrawal intervention.
abstract: Metabolic consequences of morphine dependence and withdrawal intervention have not been well explored. In the present study, the metabolic changes in brain hippocampus, nucleus accumbens (NAc), prefrontal cortex (PFC) and striatum of rats with morphine dependence and withdrawal intervention were explored by using ¹H nuclear magnetic resonance coupled with principal component analysis, partial least squares and orthogonal signal correction analysis. We found that the concentrations of neurotransmitters including glutamate, glutamine and gamma-aminobutyric acid changed differentially in hippocampus, NAc, PFC and striatum after repeated morphine treatment. Significant changes were also found in a number of cerebral metabolites including N-acetyl aspartate (NAA), lactic acid, creatine, myo-inositol and taurine. These findings indicate the profound disturbances of energy metabolism, amino acid metabolism and neurotransmitters caused by chronic morphine treatment. Interestingly, morphine-induced changes in lactic acid, creatine and NAA were clearly reversed by intervention of methadone or clonidine. Our study provides a comprehensive understanding of the metabolic alteration associated with morphine addiction and withdrawal therapy, which may help to develop new pharmacotherapies.
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.forename: Pengchi
authors.initials: P
authors.lastname: Deng
authors.forename: Qian
authors.initials: Q
authors.lastname: Bu
authors.forename: Guangyan
authors.initials: G
authors.lastname: Yan
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Zhou
authors.forename: Xue
authors.initials: X
authors.lastname: Shao
authors.forename: Jinxuan
authors.initials: J
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhu
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Xu
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009294:Narcotics; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009020:Morphine