Laboratory of Neurobiology and the State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
Behav Brain Res. 2011 Aug 1;221(1):197-206. doi: 10.1016/j.bbr.2011.03.002. Epub 2011 Mar 15.
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.
反复接触成瘾药物会导致与成瘾相关的大脑区域（如伏隔核、海马体和前额叶皮层）中的蛋白质持续甚至永久表达变化，而杏仁核中蛋白质含量的变化则很少被研究。在这里，我们旨在寻找参与吗啡诱导的条件性位置偏好（CPP）过程的蛋白质。在大鼠中建立吗啡诱导的 CPP 模型，并在吗啡诱导的 CPP 的不同阶段获得大鼠杏仁核组织：建立组、消退组、复燃组和盐水组作为对照。进行二维电泳（2-DE）分析和比较吗啡诱导的 CPP 过程中大鼠杏仁核中蛋白质表达谱的变化。与盐水组相比，杏仁核中有 80 种蛋白质的表达发生了 1.3 倍的变化，其中大多数呈下调趋势。这些差异表达的蛋白质主要涉及代谢、结构、细胞信号通路和泛素-蛋白酶体通路。并且我们进一步使用逆转录-聚合酶链反应（RT-PCR）和 Western 印迹法来验证蛋白质组学的结果。有丝分裂激活蛋白激酶 1（MAPK1）在吗啡诱导的 CPP 的消退和复燃阶段增加，而胶质纤维酸性蛋白（GFAP）在消退阶段减少。我们的结果提供了一些参与杏仁核中阿片类药物成瘾分子机制的蛋白质和细胞信号通路。
