根据本课题组已取得的实验结果，我们率先在国内外提出一个全新的学术观点，认为“阿片成瘾可能是一种与蛋白质折叠和组装相关的慢性脑病”，即“分子伴侣介导阿片成瘾(Chaperone-mediated opioid addiction)”学说。有鉴于此，本项目采用行为医学与分子药理学相结合的研究策略，选用斑马鱼和大鼠作为研究对象，建立吗啡成瘾模型（行为敏化、躯体戒断和条件性位置偏爱），针对与吗啡成瘾相关的神经核团（VTA、NAc和LC），以分子伴侣Hsp70为研究靶标，从功能活性（小分子抑制剂和诱导剂）和基因表达（Hsp70基因敲低和过表达）两个层面，阐明分子伴侣介导阿片成瘾新的分子药理学机理，进一步确证分子伴侣Hsp70可以作为治疗吗啡成瘾一个新的药理学靶点。本项目相关研究工作的开展有助于加深对阿片类药物成瘾分子药理学机制的理解，为成瘾治疗药物的研究开拓新的思路和方向。

Based on our experimental data, we firstly advance a new hypothesis at home and abroad, in which opioid addiction may be considered as a chronic brain disease related to protein folding and assembling：Theory of “Chaperone-mediated opioid addiction” . Therefore, we would carry out the program with the research strategies of behavioral medicine plus molecular pharmacology. In the program, rats and zebrafishes are used to establish the animal models of morphine addiction including behavioral sensitization, physical withdrawal syndrome and conditioned place preference. Focusing on one new molecular target chaperone Hsp70 in the addiction-related neural pathway (VTA, NAc and LC), we would investigate the molecular mechanisms underlying the chaperone-mediated opioid addiction in the aspects of Hsp70 functional profiles (small molecular inhibitors and inducers) and gene expression (knock-down and over-expression) and further determine that chaperone Hsp70 may be a potentially novel pharmacological molecular target for treating morphine addiction. Obviously, this is an important piece of research program for a better understanding of the neurobiological mechanisms behind opioid addiction and developing certain ways and directions to study some new therapeutic compounds for addiction.