为阐明双重特异性磷酸酶（dual-specificity phosphatases，DUSPs）在海洛因依赖中的作用。本研究构建海洛因依赖小鼠模型，对中脑边缘皮质系统（NAc-Hip-PFC）DUSP1-28基因进行Q-PCR检测，初步筛选脑区差异基因；通过对差异基因蛋白表达进行检测，进一步筛选发挥重要作用DUSPs基因；采用药理学及克隆慢病毒进行干预研究，检测MAPK表达及活化，筛选出DUSPs关键基因；对MAPK信号通路及其靶蛋白进行芯片检测，揭示DUSPs关键基因信号通路作用机制；采用小鼠DUSPs基因敲除模型，对依赖不同阶段行为学及信号分子进行检测，明确DUSPs关键基因信号传导机制；利用本实验室培育的小鼠多巴胺受体基因敲除模型，完善DUSPs在海洛因依赖中的上下游信号通路分子机制；模拟美沙酮维持治疗，观察关键基因及信号通路变化，为毒品依赖的防治和新药研发提供实验基础和理论依据。

To clarify the role of dual-specificity phosphatase (DUSPs) in heroin dependence, a comprehensive assessment is determined to establish the heroin dependence mice model. To find significant genetic differences between the case and control groups, the mRNA expression levels of DUSPs in the mesolimbic cortex system (NAc-Hip-PFC) are carried by Q-PCR. To screen the key genes, the protein expression levels of DUSPs are determined by Western blot and immune fluorescent. To clarify the role of key genes, the agonist/antagonist and Raav-DUSPs cloning lentivirus mice are employed in intervention study, then detect the expression of MAPK and its phosphorylation. To reveal the signaling mechanism of key genes, The MAPK signal pathway and its target proteins are detected by chip, then test the signal molecules and behaviors on different phases of DUSP-/- knockout mice ;To perfect the upstream and downstream of MAPK signaling, we employ the DRD1-/-/DRD3-/- mice. Finally, the expression of key genes and signal pathway are observed through simulating of methadone maintenance treatment. In summary, these results may provide experimental and theoretical basis for the prevention of heroin dependence and drug discovery.