生物谷报道：精神活性物质成瘾防治和戒除是本世纪人类面临的重大难题，也是近年来国际毒理学和心理学研究的热点方向。然而，这一领域的关键性问题之一——精神活性物质成瘾过程中的突触形态异常和神经生理改变的潜在分子机制不能得到准确描述，大大影响了该领域的科学进展。日前浙江大学沃森基因组科学研究院朱永平教授的博士生杨柳与中科院心理所行为遗传中心孙中生教授就这一问题展开合作，取得重要成果。本研究建立了慢性吗啡成瘾的大鼠模型来模拟人类慢性成瘾过程，并使用双向电泳和质谱来分析前额叶皮质突触相关蛋白在成瘾的各个阶段的差异改变，试图找出与成瘾各阶段相关的生物学分子标记物。研究结果表明，包括能量代谢、信号转导、突触传递、骨架蛋白、分子伴侣和突触蛋白合成器在内的6类80个差异蛋白构成了吗啡诱导的依赖、戒断和复燃的突触相关分子网络。这一结论描述并揭示了慢性吗啡暴露引起的复杂、综合的神经性适应过程，为毒品防治和戒除类药物的开发提供新的科学依据。
研究论文《Proteomic Analysis of Rat Prefrontal Cortex in Three Phases of Morphine-Induced Conditioned Place Preference（吗啡诱导条件性位置偏爱三个阶段大鼠前额叶皮质的蛋白质组学分析）》已在蛋白质组学领域的国际顶尖杂志《蛋白质组学研究》（Journal of Proteome Research） 07年4月20日的刊号上全文发表。
原始出处:
J. Proteome Res., ASAP Article 10.1021/pr060649o S1535-3893(06)00649-X
Web Release Date: April 20, 2007 Copyright © 2007 American Chemical Society
Proteomic Analysis of Rat Prefrontal Cortex in Three Phases of Morphine-Induced Conditioned Place Preference
Liu Yang, Zhong Sheng Sun, and Yong-ping Zhu*
James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Department of Toxicology, Zhejiang University, School of Medicine, Hangzhou, Zhejiang, P. R. China, and Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, P. R. China
Received December 6, 2006
Abstract:
Morphological alterations of synapse are found after morphine administration, suggesting that regulation of synaptic plasticity may be one of the mechanisms of neuroadaptation in addiction. However, the molecular basis underlying the abnormal synapse morphological and physiological changes in the morphine-induced dependence, withdraw, and relapse is not well understood. As prefrontal cortex (PFC) is one of the most important brain regions, which provides executive control over drug use and is severely impaired in many addicts, systematic analysis of the biochemical and molecular alteration of synaptic fraction of PFC in morphine-induced neuroadaptation is necessary. In this study, differential protein expression profiling of synaptic fraction of rat PFC based on morphine-induced conditioned place preference (CPP) model was performed with two-dimensional gel electrophoresis (2-DE). Our results showed that a total of 80 proteins were differentially expressed by 2-DE analysis during three phases of CPP assay. Of them, 58 were further identified by mass spectrometry. These proteins were classified into multiple categories, such as energy metabolism, signal transduction, synaptic transmission, cytoskeletal proteins, chaperones, and local synaptic protein synthetic machinery according to their biological functions. Our study provides a global view of synaptic-related molecular networking in PFC under morphine-induced dependence, withdraw, and relapse, indicative of a concerted biological process in neuroadaptation under chronic morphine exposure.
Keywords: morphine addiction conditioned place preference (CPP) prefrontal cortex (PFC) proteomics neuroplasticity
