National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
J Proteomics. 2012 Feb 2;75(4):1330-42. doi: 10.1016/j.jprot.2011.11.008. Epub 2011 Nov 16.
It has been known that the reinforcing effects and long-term consequences of morphine are closely associated with nucleus accumbens (NAc) in the brain, a key region of the mesolimbic dopamine pathway. However, the proteins involved in neuroadaptive processes and withdrawal symptom in primates of morphine dependence have not been well explored. In the present study, we performed proteomes in the NAc of rhesus monkeys of morphine dependence and withdrawal intervention with clonidine or methadone. Two-dimensional electrophoresis was used to compare changes in cytosolic protein abundance in the NAc. We found a total of 46 proteins differentially expressed, which were further identified by mass spectrometry analysis. The identified proteins can be classified into 6 classes: metabolism and mitochondrial function, synaptic transmission, cytoskeletal proteins, oxidative stress, signal transduction and protein synthesis and degradation. Importantly, we discovered 14 proteins were significantly but similarly altered after withdrawal therapy with clonidine or methadone, revealing potential pharmacological strategies or targets for the treatment of morphine addiction. Our study provides a comprehensive understanding of the neuropathophysiology associated with morphine addiction and withdrawal therapy in primate, which is helpful for the development of opiate withdrawal pharmacotherapies.
已知吗啡的强化作用和长期后果与大脑中的伏隔核（NAc）密切相关，伏隔核是中脑边缘多巴胺通路的关键区域。然而，在吗啡依赖的灵长类动物中，参与神经适应过程和戒断症状的蛋白质尚未得到充分探索。在本研究中，我们用可乐定或美沙酮对吗啡依赖和戒断干预的恒河猴的 NAc 进行了蛋白质组学研究。二维电泳用于比较 NAc 中胞质蛋白丰度的变化。我们发现共有 46 种蛋白质表达差异，进一步通过质谱分析进行了鉴定。鉴定出的蛋白质可分为 6 类：代谢和线粒体功能、突触传递、细胞骨架蛋白、氧化应激、信号转导以及蛋白质合成和降解。重要的是，我们发现可乐定或美沙酮戒断治疗后有 14 种蛋白质明显但相似地发生改变，这揭示了治疗吗啡成瘾的潜在药理学策略或靶点。我们的研究提供了对与灵长类动物吗啡成瘾和戒断治疗相关的神经病理生理学的全面理解，这有助于阿片类药物戒断的药理学治疗的发展。
