National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
J Neurosci Res. 2012 Nov;90(11):2154-62. doi: 10.1002/jnr.23109. Epub 2012 Jul 30.
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 (1) H-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), γ-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.
尚未充分探讨涉及吗啡依赖的全面脑代谢物。为了更好地了解与人高度相关的模型中的吗啡依赖和戒断治疗，通过（1）H 核磁共振波谱法结合偏最小二乘和正交信号校正分析，测量恒河猴海马体和前额叶皮层（PFC）的代谢变化。结果表明，吗啡依赖猴海马体和 PFC 中的肌醇（M-Ins）和牛磺酸浓度显著降低，而乳酸增加。慢性吗啡治疗后，磷酸胆碱和肌酸在 PFC 中增加，而在海马体中减少。此外，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酸也在这些脑区发生变化。这些结果表明，慢性吗啡暴露会导致大脑中的神经递质、膜和能量代谢发生深刻紊乱。值得注意的是，美沙酮或可乐定干预后，NAA、肌酸、乳酸、牛磺酸、M-Ins 和磷酸胆碱的吗啡诱导失调明显逆转。我们的研究强调了代谢组学的潜力，可以增强我们对与灵长类动物吗啡成瘾和戒断治疗相关的代谢物改变和神经生物学作用的理解。
