Rothman R B, Glowa J R
Clinical Psychopharmacology Section, IRP, NIDA, NIH, Baltimore, MD 21224, USA.
Mol Neurobiol. 1995 Aug-Dec;11(1-3):1-19. doi: 10.1007/BF02740680.
Medication development for cocaine abuse has focused on potential mechanisms of action related to the abuse of cocaine. The hypothesis that mesolimbic dopamine (DA) is the key neurochemical mediator of cocaine's addictive and reinforcing effects is well supported by a wide variety of data from animal studies. On the other hand, medications that increase DA or block its action in humans can produce effects that appear incompatible with this hypothesis. This article reviews these incompatibilities between animal and human data with a focus on the DAergic actions of drugs, including DA reuptake inhibitors, direct DA agonists, DA increasers, and DA antagonists. Possible reasons for these discrepancies are discussed, and the potential role of high-affinity DA uptake inhibitors, such as GBR12909, for pharmacotherapies for treating cocaine addiction in humans is likely to come from understanding its mechanisms of action, it is clear that further research on the effects of cocaine in humans and animals will be critical to the medication development effort.
针对可卡因滥用的药物研发主要集中在与可卡因滥用相关的潜在作用机制上。中脑边缘多巴胺（DA）是可卡因成瘾和强化作用的关键神经化学介质这一假说，得到了来自动物研究的大量数据的有力支持。另一方面，在人类中增加DA或阻断其作用的药物所产生的效应，似乎与该假说并不相符。本文回顾了动物和人类数据之间的这些不相符之处，重点关注药物的多巴胺能作用，包括DA再摄取抑制剂、直接DA激动剂、DA增强剂和DA拮抗剂。讨论了这些差异的可能原因，高亲和力DA摄取抑制剂（如GBR12909）在人类可卡因成瘾药物治疗中的潜在作用，可能源于对其作用机制的理解，很明显，对可卡因在人类和动物中的作用进行进一步研究，对于药物研发工作至关重要。
