Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland.
Basic Clin Pharmacol Toxicol. 2011 Jan;108(1):2-8. doi: 10.1111/j.1742-7843.2010.00647.x. Epub 2010 Nov 30.
During the last 15 years, genetically modified mouse lines have proved to be a valuable research tool. This review summarizes research that studied addiction-like behaviour in mice that had a targeted mutation in the genes of the synaptic dopamine removal systems, i.e. in the dopamine transporter (DAT), a vesicular monoamine transporter 2 (VMAT2) or two dopamine-metabolizing enzymes (monoamine oxidase, MAO, mainly MAO-A isoenzyme, and catechol-O-methyltransferase, COMT). Majority of the mice are knockouts but also some knock-in and knock down mouse lines are included. Most studies have explored DAT, and it has been shown to be the critical target in addiction to psychostimulants. Its role in the development of addiction-like behaviour to nicotine, opioids or ethanol is less clear. VMAT2 also seems to be linked to psychostimulant addiction. MAO-A and COMT have a minor role in addiction-like behaviour that is further complicated by a sexual dimorphism.
在过去的 15 年中，基因修饰小鼠品系已被证明是一种有价值的研究工具。本综述总结了研究靶向突变突触多巴胺清除系统基因（即多巴胺转运体（DAT）、囊泡单胺转运体 2（VMAT2）或两种多巴胺代谢酶（单胺氧化酶，MAO，主要是 MAO-A 同工酶，和儿茶酚-O-甲基转移酶，COMT））导致类似成瘾行为的小鼠的研究。大多数小鼠是基因敲除品系，但也包括一些基因敲入和基因敲低的小鼠品系。大多数研究都探讨了 DAT，表明其是对精神兴奋剂成瘾的关键靶点。其在尼古丁、阿片类药物或乙醇所致类似成瘾行为的发展中的作用尚不明确。VMAT2 似乎也与精神兴奋剂成瘾有关。MAO-A 和 COMT 在类似成瘾行为中的作用较小，但存在性别二态性，使其更加复杂。
