Galanin system在吗啡成瘾记忆中的作用机制

The drugs are very harmful to users, their families as well as the society, and the rate of criminal crime caused by drug abuse has been in a high level. However, until today, to elucidate the mechanism of drug addiction is still a big challenge for the forensic toxicologists and neuroscientists. From perspective of learning and memory, the formation of drug addictive behavior is a aberrant process of learning and memory. Drug memory plays an important role in addictive behavior. Previous studies showed that the galanin system was implicated in drug addiction and learning and memory separately. Based on these findings, we suggest a hypothesis: galanin is necessary, at least to some degree, for the processes of drug memory. Our completed research provides the evidence that galnon, a galanin receptor 1 and 2 agonist, can significantly facilitate the extinction process of drug memory. In this proposal, we will try to know how the galanin system influence the different processes of drug memory, which signaling pathway participates in and which brain areas play the key role; simultaneously, we also compare the differences between the processes of normal memory and drug memory; and our ultimate goal is to find out the valuable targets for the interruption of drug memoy and give some new ideas and methods for the mechanism of drug addiction.

毒品对使用者本人、家庭和社会的危害极大，吸毒引发的刑事犯罪率长期居高不下。阐明毒品成瘾的机制仍然是法医毒物学和神经科学基础研究长期面临的重要难题。既往研究表明，毒品成瘾行为的形成是一种异常的学习记忆过程，成瘾记忆在成瘾行为形成中扮演着极为重要的角色。业已证明，galanin system分别参与了毒品成瘾和学习记忆两种过程，申请人团队的研究显示：galanin受体1和2的共同激动剂--galnon可明显地促进成瘾记忆的消退过程，印证了我们提出的galanin system可能在成瘾记忆的形成过程中发挥了重要作用的假设。基于此，本次申请的课题将全面、系统地阐明galanin system及其下游信号通路在成瘾记忆的各个阶段、各主要脑区所发挥的作用，同时与正常的学习记忆模式进行比较，找出干预成瘾记忆的相关靶点，为毒品成瘾机制的研究提供新的思路和方法。

本项目以脑内galanin system为靶标，研究其在毒品成瘾病理性记忆形成过程中的发挥作用的机制，以期为毒品成瘾的治疗提供新思路。我们发现galnon 作为galanin 受体的广谱激动剂，可明显促进吗啡诱导成瘾记忆的消退过程，其中Nac脑区发挥关键作用。在该脑区galanin受体的表达异常，伴随单胺类系统失衡可能作为内在机制参与其中。并发现提高galanin受体2在Nac脑区的表达水平，以及相应增加去加肾上腺自身受体α2A受体的表达，对成瘾治疗有益。在项目支持下，发表20余篇学术论文，以部分研究内容参与获得陕西省科技进步2等奖1项，培养毕业博士研究生4名，硕士生2名。