腹侧海马区(Ventral hippocampus,vHP)是学习和记忆药物相关线索（Context/Cue）信息的关键结构，该通路所发生的病理性神经适应性变化是可卡因戒断后产生复吸现象的关键原因之一。miR-134参与调控海马的神经元成熟和可塑性的构建，以及调节海马区相关脑病的病理发生过程。本项目拟采用可卡因相关线索诱发可卡因复吸的大鼠模型，观察vHP区miR-134在可卡因接触不同阶段(长期暴露，戒断或熄灭觅药，恢复觅药)的表达变化；利用局部沉默miR-134和过表达miR-134的技术，观察vHP区miR-134对可卡因复吸行为的影响；从靶基因筛选、海马突触微结构重建、海马区电生理活动、海马与其他成瘾脑区关联性四个方面，探索vHP区miR-134影响可卡因复吸行为的神经机制。本项目研究结果将有助于进一步理解可卡因复吸行为的分子生物机制，为预防复吸和戒毒治疗的新药开发提供了新的思路。

Ventral hippocampus (vHP) is thought to be involved in the process of context-(or cue-) and rewarding-associated learning and memory. Neuroadaptaion induced by cocaine exposure in vHP are believed to contribute to the development of cocaine relapse behavior. Recently, miR-134 is reported to take part in the processes of neuron mature, synaptic remolding and plasticity in hippocampus. In addition, miR-134 is found to be involved in regulating the development of hippocampus-related brain diseases. The current study is designed to explore the role of miR-134 on vHP in cocaine context (or cue)-induced relapse behavior. First, the expressions of miR-134 during several cocaine exposures (repeated cocaine exposure, cocaine withdrawal or extinction, and reinstatement) are examined in the subregions of vHP. Then, the effects of local knockdown or overexpresision of miR-134 in vHP on the reinstatement of cocaine-seeking behavior is explored using cocaine conditioned place preference (CPP) rat model and cocaine self-administration (SA) rat model. Last, the molecular and cellular mechanisms underlying the regulating role of miR-134 in cocaine relapse behavior is investigated from the following aspects: (1) Identification of target genes for miR-134 in vHP; (2) Regulating effects of miR-134 on synaptic pasticity in vHP; (3) Regulating effects of miR-134 on electrophysiological activity in vHP; (4) Regulating effects of miR-134 on the interaction between vHP and ventral tegment area (VTA), the other brain region targeted by cocaine abuse. The results of this study will help to better understand molecular and cellular mechanisms of drug abuse and may provide new targets for the development of therapeutic agents against drug addiction.