酒依赖治疗的重点是戒断后的复饮。成瘾性物质反复使用与药物的使用环境可以形成关联性记忆，记忆唤起-消退范式可以消除药物成瘾者的成瘾记忆，进而降低心理渴求，减少复吸行为的发生。然而该范式对降低酒依赖患者的心理渴求是否有效尚不清楚，清醒状态下暴露酒精相关的线索极易诱发复饮，临床效果不佳。我们的预试验结果提示，睡眠状态下应用唤起-消退范式可以降低酒依赖患者的心理渴求，减少其情绪反应，避免了复饮的直接诱发，提高了临床实践的可行性。申请人拟选择酒依赖患者为研究对象，探索唤起-消退范式对降低酒依赖患者心理渴求的作用及其神经影像学机制；利用大鼠酒精自我给药模型探索相关脑区，如前额叶皮层、杏仁核、腹侧被盖区和伏隔核等的功能活动调控觉醒和睡眠状态下唤起-消退范式影响记忆表达的过程，阐述单胺类神经递质介导的神经微环路参与记忆调节的神经机制，为临床开发新型安全的无创消除酒依赖患者心理渴求的新范式提供理论基础。

The key point in clinical treatment of alcohol dependence is relapse. Addictive substance and relevant environment form association memory, memory retrieval-extinction paradigm can erase addictive memory, reduce craving and relapse. But the effect of retrieval-extinction paradigm on alcohol-related memories is still unclear. Moreover, exposure of alcohol-related cues under wakefulness may elicits relapse easily. Our pilot study has found that retrieval-extinction paradigm applied during sleep suppresses craving without interfering emotional response and avoids of relapse. Then, we hypothesize that retrieval-extinction paradigm under sleep can reduce cues-induced craving and improve the feasibility. In this project, we will use alcohol addicts to elucidate the role of retrieval-extinction paradigm in alcohol dependence and its mechanisms of neuroimaging. We will also use animals models of addiction to investigate the functional activity of reward memory-related brain areas (prefrontal cortex, Amygdala, ventral tegmental area, nucleus accumbens, etc.) underlying retrieval-extinction paradigm applied during sleep and wakefulness effect on memory expression. The neural micro-loop mechanism mediated by monoamine neurotransmitters remains to be further tested. Finally, our study aims to provide the theoretical basis for developing new and safe and non-invasive clinical therapy of erasing craving in alcohol dependence.