1H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus monkeys with morphine treatment and withdrawal intervention
1H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus monkeys with morphine treatment and withdrawal intervention
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DOI：
10.1002/jnr.23109
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发表时间：
2012-11-01
影响因子：
4.2
通讯作者：
Cen, Xiaobo
中科院分区：
文献类型：
--
作者：
Deng, Yi;Bu, Qian;Cen, Xiaobo
与吗啡依赖相关的大脑综合代谢物尚未得到充分研究。为了在与人类高度相关的模型中更好地理解吗啡依赖及戒断治疗，通过氢-1核磁共振波谱法，并结合偏最小二乘法和正交信号校正分析，对恒河猴大脑海马体和前额叶皮质（PFC）的代谢变化进行了测定。结果显示，吗啡依赖猴的海马体和前额叶皮质中，肌醇（M-Ins）和牛磺酸浓度显著降低，而乳酸浓度升高。长期使用吗啡后，前额叶皮质中的磷酸胆碱和肌酸增加，而海马体中的则减少。此外，这些脑区中的N-乙酰天冬氨酸（NAA）、γ-氨基丁酸、谷氨酸、谷胱甘肽、蛋氨酸和高半胱氨酸也发生了变化。这些结果表明，长期接触吗啡会对大脑中的神经递质、膜和能量代谢造成严重干扰。值得注意的是，使用美沙酮或可乐定进行干预后，吗啡诱导的NAA、肌酸、乳酸、牛磺酸、M-Ins和磷酸胆碱的失调明显得到逆转。我们的研究强调了代谢谱分析在增进我们对灵长类动物吗啡成瘾及戒断治疗相关的代谢物改变和神经生物学作用理解方面的潜力。（c）2012 威利期刊公司
Comprehensive cerebral metabolites involved in morphine dependence have not been well explored. To gain a better understanding of morphine dependence and withdrawal therapy in a model highly related to humans, metabolic changes in brain hippocampus and prefrontal cortex (PFC) of rhesus monkeys were measured by 1H-nuclear magnetic resonance spectroscopy, coupled with partial least squares and orthogonal signal correction analysis. The results showed that concentrations of myoinositol (M-Ins) and taurine were significantly reduced, whereas lactic acid was increased in hippocampus and PFC of morphine-dependent monkeys. Phosphocholine and creatine increased in PFC but decreased in hippocampus after chronic treatment of morphine. Moreover, N-acetyl aspartate (NAA), ?-aminobutyric acid, glutamate, glutathione, methionine, and homocysteic acid also changed in these brain regions. These results suggest that chronic morphine exposure causes profound disturbances of neurotransmitters, membrane, and energy metabolism in the brain. Notably, morphine-induced dysregulations in NAA, creatine, lactic acid, taurine, M-Ins, and phosphocholine were clearly reversed after intervention with methadone or clonidine. Our study highlights the potential of metabolic profiling to enhance our understanding of metabolite alteration and neurobiological actions associated with morphine addiction and withdrawal therapy in primates. (c) 2012 Wiley Periodicals, Inc.