药物戒断产生的躯体不适与戒断时所处的情景线索关联后会形成持久的戒断记忆。后期情景线索可通过激活特定神经环路来提取戒断记忆，促进觅药行为的产生。因此研究长期情景相关戒断记忆的形成机制对于减少复吸非常重要。记忆信号从海马向皮层的转移是长期记忆形成的关键步骤。我们应用吗啡戒断条件位置厌恶模型研究发现：投射到前扣带回（ACC）的海马CA3神经元介导了情景相关戒断记忆从海马CA3向ACC的转移；并且ACC神经元Arc蛋白的表达和树突棘增加也参与了记忆的转移。但在此过程中CA3神经元发生何种变化，通过何种机制影响ACC神经元还不清楚。我们的假说认为：行为训练后形成的CA3印迹神经元主要通过持续释放谷氨酸递质作用于ACC神经元，促其转变为成熟的印迹神经元，完成情景相关戒断记忆从海马CA3向ACC的转移。本项目将运用多种技术手段对此假说机制进行详细论证，这对于了解长期情景相关戒断记忆的形成机制十分重要。

Drug withdrawal induced physical discomfort can associate with episodic cues to form remote withdrawal memory. Similar episodic cues can reactivate specific neural circuits to retrieval withdrawal memory and promote drug-seeking behavior. So it is important to study the mechanism of remote episodic withdrawal memory for reduce relapse. The transfer of recent memory from the hippocampus to cerebral cortex is a key step in the formation of remote memory. Using morphine withdrawal conditioned place aversion model, we found that the ACC targeted hippocampal CA3 neurons mediate the transfer of episodic withdrawal memory from the hippocampus to ACC. In addition, the Arc protein and the increase of dendritic spines of ACC neurons are involved in this process. However, what changes occur in hippocampal CA3 neurons and how they affect ACC neurons are unclear. Our hypothesis is that hippocampal CA3 engram neurons formed after behavioral training can release excitatory glutamate to act on ACC neurons during the process of memory transfer, and this persistent excitatory inputs promote the functional maturity of ACC engram neurons to complete the transfer of episodic withdrawal memory from hippocampal CA3 to ACC.