¹H NMR-based metabonomic analysis of brain in rats of morphine dependence and withdrawal intervention

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• 作者：Zhengtao Hu^a ; ¹ ; Yi Deng^a ; ¹ ; Chunyan Hu^a ; Pengchi Deng^b ; Qian Bu^a ; Guangyan Yan^a ; Jiaqing Zhou^a ; Xue Shao^a ; Jinxuan Zhao^a ; Yan Li^a ; Ruiming Zhu^a ; Youzhi Xu^a ; Yinglan Zhao^a ; Xiaobo Cen^a ; ^{xbcenalan@sina.com}
• 关键词：CPMG ; Carr-Purcell-Meiboom-Gill ; FIDs ; free induction decays ; GABA ; gamma-aminobutyric acid ; GAD ; glutamic acid decarboxylase ; M-Ins ; myo-inositol ; NAA ; N-acetyl aspartate ; NAc ; nucleus accumbens ; NMDA ; N-methyl-d-aspartate ; NMR ; nuclear magnetic resonanc
• 刊名：Behavioural Brain Research
• 出版年：2012
• 期刊代码：3_01664328
• 类别：neu
• 出版时间：16 May, 2012
• 卷：231
• 期：1
• 页码：11-19
• 文件大小：1037 K

摘要

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.