ΔFosB及其上游信号转导通路的调控机制及其人工干预对MA慢性依赖小鼠行为学变化的影响

药物依赖是一种由滥用药物与大脑奖赏系统相互作用产生的慢性复发性脑疾病，已成为医学研究领域的热点和难点问题。我们在国内外药物依赖机制研究基础上，以中枢神经系统神经元内转录因子ΔFosB这一关键分子开关作为研究突破点，着重分析从细胞外药物刺激作用，到转录因子ΔFosB高水平长时程持续存在这一过程，研究依赖性药物诱导的中枢神经系统的结构性重塑、生物个体的行为敏化这一结果的发生发展机制。同时利用人工干预手段，如中枢神经内主要的磷酸激酶CK2抑制剂，来观察MA慢性依赖动物ΔFosB及其上游调控通路关键分子的结构功能改变与成瘾动物行为变化的关系，以期能够找到阻断药物慢性依赖的关键分子。并进一步通过对这些必要关键分子的人工干预，来达到人为调控神经信号转导通路，从而抑制神经系统的长时程可塑性改变，减弱甚至逐渐消除药物所致的精神运动异常；同时该研究对阐明药物慢性依赖的分子机制及寻找治疗手段等方面具有重要意义

Drug addiction is a chronic, relapsing disease that result from the prolonged effects of drugs on the brain. It has become a hotspot and difficult problem in medical research. On the basis of prior mechanism research of drug addiction, we choose an one of the vital transcription factors ΔFosB , which is the key molecular switch, in the central nervous system as the research breakthrough, focus on the high level and prolonged persist of ΔFosB changes and research the occurrence and development mechanism of the structural remodeling and behavioral sensitization induced by MA chronic addiction. At the same time, by using the manual intervention methods, such as the phosphokinase CK2 inhibitor, we observe relationship between ΔFosB changes and its upstream signal transduction pathways in MA chronic addiction mouse and its behaviour changes, to find a key molecule which could block the drug addiction. At last, by manual intervention regulating the key molecule we could inhibit the prolonged neural plasticity changes and to recede even remove the abnormal mental movements resulted from the drug. The research has a very important meaning for clarifying the molecular mechanism and searching a therapeutic method of chronic drug addiction .