藥物成癮的過程會造成人類腦部永久性且不可逆的傷害，現已成為世界上日益關切的問題。而在眾多違禁藥物中，甲基安非他命(神經興奮性藥物)與海洛因(鴉片類止痛鎮定藥物)，會對多巴胺神經傳遞系統產生神經毒性，從而導致藥物使用上的耐受性以及生理上的依賴性。雖然在哺乳動物大腦中許多影響藥物成癮過程的因子及藥物誘導基因表現上的改變已被分析得到，但藉由比較長期藥物濫用之後，蛋白質間交互作用的動態網路，可以從系統的觀點上提供藥物成癮發展過程中新的見識。在本文研究中，我們以蛋白質間交互作用相關資訊以及基因動態表現數據為根據，透過使用動態模型分別建構在慢性投予生理食鹽水，甲基安非他命與海洛因後的三組蛋白質交互作用網路。隨後，我們從投予甲基安非他命與海洛因對比於投予生理食鹽水的蛋白質交互作用網路，比較網路結構與蛋白質之間調控的不同，並且估算每個蛋白質交互作用對象的總改變(TCI)以及交互能力上的差異(DIA)，藉此找到分別在甲基安非他命與海洛因成癮過程中可能扮演重要角色的蛋白質。而此比較方法除了可以作為臨床或學術實驗前的篩選工具，用以找出值得更進一步探討的新蛋白質外，並藉此了解藥物成癮過程的相關機制，進而成為藥物成癮干預療法的起點。

Drug addiction, a growing problem worldwide with recent concerns, results in long-lasting harmful effects to the human brain. Methamphetamine (MA) and Heroin (HER) are illicit drugs known to exert neurotoxic effects on the dopaminergic systems leading to the development of tolerance and physical dependence. Although many factors affecting addictive processes and drug-induced gene expression changes in the brain have been analyzed, comparing protein-protein interaction (PPI) networks exposure to drugs of abuse may provide new insights into the development of addiction from the systematic point of view. In this study, based on PPI information and gene expression profiles, a dynamic model is employed to reconstruct three PPI networks corresponding to chronic treatment with saline (SAL), MA, and HER, respectively. Subsequently, we compare the difference of network structure and compute the total changed interactions (TCI) and differential interactive ability (DIA) from MA-treated and HER-treated PPI networks versus SAL-treated PPI network to discover potential proteins that play critical roles in MA and HER addictive process, respectively. This comparison method can be employed as a pre-experiment screening approach to reveal new potential proteins for further characterization to understand the underlying mechanisms in addictive process, serving as the starting point of therapeutic intervention for drug addiction.

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