Chiu Veronica M, Schenk James O
Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
Curr Drug Abuse Rev. 2012 Sep;5(3):227-42. doi: 10.2174/1874473711205030227.
Addiction to methamphetamine (METH) is thought to be mediated by dopaminergic effects in the reward pathway in the brain via the A10 dopaminergic pathway. Herein we describe an overview of the results of the basic preclinical science undertaken to provide mechanistic insights into the action of amphetamines in general and METH in particular. A brief history of amphetamine and METH use and abuse is given, and an overview of the relevant chemical aspects of amphetamine as they relate to neurotransmitters in general is made. A review of the methods used to study the biochemical effects of METH is outlined. Finally, a focused analysis of the kinetic mechanisms of action of the amphetamines in general, and METH in particular, at the transmembrane transporters and at the intracellular vesicular storage sites is made. A description of how catecholaminergic and serotonergic nerve signaling may be altered by METH is proposed. Overall, the emphasis here is on differences in effects observed between the striatal (the A9 substantia nigral dopamine pathway) and nucleus accumbens (the A10, ventral tegmental pathway) areas of the brain following acute as well as repeated dosing and withdrawal.
甲基苯丙胺（METH）成瘾被认为是通过A10多巴胺能通路在大脑奖赏通路中产生的多巴胺能效应介导的。在此，我们概述了基础临床前科学研究的结果，以深入了解安非他明尤其是METH的作用机制。介绍了安非他明和METH使用及滥用的简史，并概述了安非他明与一般神经递质相关的化学方面。概述了用于研究METH生化效应的方法。最后，重点分析了一般安非他明尤其是METH在跨膜转运体和细胞内囊泡储存位点的作用动力学机制。提出了关于METH如何改变儿茶酚胺能和5-羟色胺能神经信号的描述。总体而言，这里重点关注急性及重复给药和戒断后，大脑纹状体（A9黑质多巴胺通路）和伏隔核（A10腹侧被盖通路）区域观察到的效应差异。
