组蛋白乙酰化是组蛋白重要的修饰方式，已成为研究药物成瘾记忆新的视角。我们前期发现，腹外侧眶皮层（VLO）是调控吗啡成瘾记忆的重要核团，VLO组蛋白H3K9乙酰化（aceH3K9）参与吗啡诱导的大鼠行为敏化的调控，但其确切的调控机制尚不清楚。本课题建立大鼠条件性位置偏爱（CPP）模型模拟吗啡成瘾记忆过程，观察成瘾不同阶段VLO内神经元突触超微结构变化及aceH3K9的mRNA、蛋白表达；利用脑立体定位术在VLO内注射慢病毒载体，过表达/干扰aceH3K9的表达，观察CPP不同阶段动物行为学、VLO内突触超微结构及记忆相关基因的变化；在VLO内注射与成瘾密切相关的多巴胺受体（DR）的激动剂/拮抗剂，检测DR-ERK通路、aceH3K9的表达及其在VLO内的共表达定位。本课题将阐明VLO组蛋白H3K9乙酰化调控吗啡成瘾记忆的作用机制，也将为寻找吗啡成瘾治疗的新靶点提供理论依据。

Histone acetylation is an important way of histone modifications which has become a new research perspective of drug addiction memory. Our recent results suggested that the ventrolateral orbital cortex (VLO) as a crucial brain region which involved in the regulation of morphine addiction. The histone H3 lysine 9 acetylation (aceH3K9) in the VLO has been found to be participated in the modulation of morphine-induced behavioral sensitization, but the roles of aceH3K9 in the VLO on morphine addiction memory and its mechanism is still not clearly understood. The present study using a rat model of morphine-induced conditioned place preference (CPP) simulates the environmental cues memory. Obtain the correlative changes of synaptic plasticity in the VLO neurons by using the transmission electron microscope. Detect the expression of aceH3K9 by using RT-PCR, Western blot. Construct lentiviral over-expression and interference vectors which were microinjected into the VLO is to manipulate the expression of aceH3K9 during different stages of morphine addiction. Observe the correlative behavior changes, ultrastructural changes in VLO' synapses and expression of memory-related genes identify the regulatory effects of aceH3K9 on addiction memory. The agonist and antagonist which are microinjected into the VLO to activate or inhibit the dopamine receptor (DR), detecting the expression of DR-ERK pathway and aceH3K9 in the VLO. The present study will not only clarify the molecular mechanisms of aceH3K9 in the VLO underlying morphine addiction memory, but also provide valuable experimental evidence and theoretical basis for the development of new treatment target in morphine addiction.