伏隔核神经元结构和功能可塑性改变是毒品成瘾的重要生物学基础，但其确切的机制尚不清楚，我们前期的研究结果提示，miR-29/Dnmt3/Meg3通路在此过程中可能参与了重要作用，因此，本研究拟利用慢病毒核团注射技术，建立相关分子过表达及表达抑制的甲基苯丙胺（METH）行为敏化小鼠模型，同时应用METH干预原代中脑神经元，采用RT-PCR、Western blot、重亚硫酸盐测序等分子生物学研究方法以及透射电镜、膜片钳等形态学和电生理研究手段，系统观察伏隔核以及培养细胞中miR-29、Dnmt3、Meg3的表达和可塑性改变及其对Meg3的靶基因Dlk1的影响，分析miR-29、Dnmt3、Meg3之间的相互作用，进一步探讨miR-29/Dnmt3/Meg3通路通过调节Dlk1并作用于Notch信号通路在METH诱导的行为敏化过程中的作用机制，为进一步揭示METH成瘾的神经生物学机制奠定基础。

Persistent changes in behavior and psychological function that occur in addicts are thought to be due to the structural and functional plasticity of neurons and synapses in the nucleus accumbens (NAc) yet the underlying mechanism remains unclear. Our previous studies suggested that miR-29/Dnmt3/Meg3 pathway may involved in methamphetamine (METH) addiction. Therefore, we aim to examine the effects of miR-29/Dnmt3/Meg3 pathway on METH-induced behavior sensitization and the underlying mechanism in the current study to further elucidate the neurobiological mechanisms of methamphetamine addiction. Firstly, we examine the changes of miR-29, Dnmt3, Meg3, Dlk1 and Notch1 in the NAc of METH-sensitized mice using RT-PCR, Western blot, and bisulfite sequencing. We then conduct miR-29, Dnmt3 and Meg3 overexpression and knockdown mice and neuronal primary culture receptively by microinjection or cell transfection of related lentivirus. Transmission electron microscope (TEM) and patch clamping technique are then used to examine the effects of miR-29/Dnmt3/Meg3 pathway as well as its downstream target gene (Dlk1) and signal pathway (Notch) on METH-induced structural plasticity and synaptic plasticity.