表观遗传调控的海马突触结构可塑性的改变在大鼠海洛因渴求和复吸中的作用及其机制研究

阿片类物质依赖是一种以复吸为主要特征的慢性脑病，目前的治疗药物主要针对躯体依赖和戒断症状，对药物成瘾的核心症状——精神依赖，包括药物渴求和复吸却无能为力。因此，深入探究阿片类物质的精神依赖机制并寻找有效治疗靶点具有重要意义。海马是负责学习记忆的重要脑区，研究表明背侧海马在药物成瘾和环境诱导的复吸中的发挥重要作用，但相关分子机制仍不清楚。阿片类物质成瘾会导致特定脑区蛋白表达改变，这些蛋白变化通过影响神经元突触可塑性最终导致药物成瘾病理性记忆形成。成瘾引起的基因和蛋白表达改变可能受表观遗传机制调控。组蛋白乙酰化，甲基化和DNA甲基化修饰是药物成瘾记忆过程中调控相关基因转录的重要机制。与组蛋白修饰相比，DNA甲基化是一种更稳定的表观遗传修饰，可能与异常牢固而持久的成瘾病理性记忆形成密切相关，因此本研究拟采用大鼠海洛因自身给药模型研究海马DNA甲基化是否参与调节大鼠的成瘾行为，并深入研究其机制。

Drug addiction is a chronic replapsing disorder that is characterized by compulsive drug seeking and taking. Hippocampus is one of the most important limbic regions that are involved in learning and memory. Previous studies have demonstrated that dorsal hippocampus plays a critical role in drug seeking and context-induced relapse behaviors, however, the underlying mechanism is unclear. Repeated exposure to opiates produces sustained abnormalities in protein expression, which induces changes in synaptic plasticity and eventually contributes to long-lasting addiction memory. These neuroadaptions can be regulated by epigenetic modifications such as histone modification, DNA methylation, or micro RNAs. To date, most reports have focused on studying histone modification in regulating addiction processes, the effects of DNA methylation have received less attention. Thus, in the present study, we will investigate whether DNA methylation is required for heroin self-administration behaviors. This study will give insights into the mechanism of drug addiction.