Changes of protein expression profiles in the amygdala during the process of morphine-induced conditioned place preference in rats

Changes of protein expression profiles in the amygdala during the process of morphine-induced conditioned place preference in rats
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吗啡诱导大鼠条件性位置偏爱过程中杏仁核蛋白表达谱的变化

DOI:
10.1016/j.bbr.2011.03.002
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发表时间:
2011-08-01
影响因子:
2.7
通讯作者:
Yu, Long-Chuan
Yu, Long-Chuan
中科院分区:
心理学3区
文献类型:
--
作者:
Lin, XiaoJing;Wang, QingSong;Yu, Long-Chuan

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成瘾性药物反复暴露可导致成瘾相关脑区(如丘脑核、海马和前额叶皮质)蛋白质表达的持续性甚至永久性变化,而杏仁核蛋白质含量的变化研究较少。本研究旨在寻找参与吗啡诱导条件性位置偏爱(CPP)过程的蛋白质。建立大鼠吗啡CPP模型,取吗啡CPP建立、消退、恢复不同阶段大鼠杏仁核组织,生理盐水对照组。采用双向电泳技术分析比较吗啡诱导大鼠位置偏爱过程中杏仁核蛋白质表达谱的变化。杏仁核中有80个蛋白质的表达量是生理盐水组的1.3倍,其中大部分蛋白质表达下调。这些差异表达蛋白主要涉及代谢、结构、细胞信号通路和泛素-蛋白酶体通路。并进一步采用逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹法对蛋白质组学结果进行了验证。有丝分裂活化蛋白激酶1(MAPK 1)在吗啡诱导CPP消退和恢复阶段表达增加,而胶质细胞酸性蛋白(GFAP)在消退阶段表达减少。我们的结果提供了一些参与杏仁核阿片类药物成瘾分子机制的蛋白质和细胞信号通路。(C)2011 Elsevier B. V.保留所有权利。
Repeated exposures to addictive drugs result in persistent or even permanent expression changes of proteins in addiction-related brain regions, such as nucleus accumbens, hippocampus and prefrontal cortex while the changes of protein content in amygdala were seldom studied. Here we aimed to find the proteins involved in the process of morphine-induced conditioned place preference (CPP). The model of morphine-induced CPP was established in rats and the rat amygdala tissues were obtained in different stages of morphine-induced CPP: establishment group, extinction group, reinstatement group and saline group as a control. Two-dimensional electrophoresis (2-DE) was performed to analyze and compare the changes of protein expression profiles in the amygdala of rats during the process of morphine-induced CPP. There were eighty proteins with 1.3-fold changes in amygdala relative to saline group, most of which were down-regulated. These differentially expressed proteins were mainly involved in metabolism, structure, cell signaling pathway and ubiquitin-proteasome pathway. And we further used methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting to confirm the results of proteomics. Mitosis activated protein kinase1 (MAPK1) was increased in the stages of extinction and reinstatement of morphine-induced CPP, while glial fibrillary acidic protein (GFAP) was decreased in the stage of extinction. Our results provide some proteins and cellular signaling pathways involved in the molecular mechanisms of opioid addiction in amygdala. (C) 2011 Elsevier B.V. All rights reserved.