我国苯丙胺类兴奋剂（ATS）的滥用形式日趋严重，引发严重社会问题、带来沉重医疗负担。本研究针对ATS成瘾过程中规律性用药阶段的核心神经学机制，拟构建给药系统能够特异性吸附并代谢突触间隙过量表达的多巴胺（DA），逆转ATS渴求。在本研究中，从肝和脑中提取纯化对DA具有高效代谢活性的膜结合型儿茶酚-O-甲基转移酶（MB-COMT），利用分子印迹技术和酶固定化技术，以DA分子印迹微球作为固相载体，引入6-碳间隔臂和MB-COMT合成分子印迹-固相生物催化型给药系统，体外优化其对DA的选择性吸附性能和专属性酶代谢活性，并在小鼠甲基苯丙胺静脉自身给药模型和甲基苯丙胺诱导的条件性位置偏爱模型中，对成瘾小鼠的行为学和神经化学影响进行系统评价。该系统可生物降解，对DA具有专属性分子识别和代谢作用，预期能够高度专一、有效的清除未被神经元重吸收的DA，为ATS成瘾治疗剂的设计提供研究基础。

The abuse of amphetamine-type stimulants (ATS) in our country is becoming more and more serious, triggering serious social problems and bringing heavy medical burdens. This study is aimed at the core neurological mechanism of the regular drug use stage in ATS addiction. It is suggested that a drug delivery system, which is capable of specifically adsorbing and metabolizing over-expression dopamine (DA) in the synaptic cleft, should be constructed and can reverse the ATS craving. In this study, membrane-bound catechol-O-methyltransferase (MB-COMT), which has highly metabolic activity for DA, is extracted from liver and brain tissue. Making use of molecular imprinting and enzyme immobilization technology, the molecular imprinting-solid phase biocatalytic drug delivery system is synthesized by utilizing DA molecular imprinting microspheres as the solid phase carriers and introducing with 6-carbon spacer arms and MB-COMT. The selective adsorption property and specific enzyme metabolic activity are optimized in vitro. In the methamphetamine self-administration model and methamphetamine-induced conditioned place preference model, the behavioral and neurochemical influences of the drug delivery system on the methamphetamine addiction are evaluated. This drug delivery system is biodegradable and has special molecular recognition and metabolic effect for DA, which is expected to achieve a highly specific and effective removal of DA that is not reabsorbed by neurons. The study provides a research basis for the design of ATS addictive therapeutic agents.