Mello N K, Negus S S
Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, MA 02178, USA.
Neuropsychopharmacology. 1996 Jun;14(6):375-424. doi: 10.1016/0893-133X(95)00274-H.
Drug abuse is a major public health problem, and the relationship between intravenous drug abuse and AIDS underscores the need for more effective treatment medications. Animal models of drug self-administration are useful to systematically evaluate new treatment medications and predict clinical efficacy. This review summarizes the status of preclinical evaluations of medications for treatment of cocaine and opiate abuse. The basic drug self-administration methodology and the rationale for experimental designs and outcome criteria are described. Studies of the effects of dopamine or opioid receptor agonists and antagonists as well as medications used clinically for other indications on drug self-administration are critically examined. Where possible, the degree of concordance between clinical and preclinical studies of drug abuse treatment medications is discussed. We conclude that drug self-administration models are valuable for preclinical assessment of medication efficacy, and we recommend some strategies to further improve evaluation procedures. The discovery of more effective medications for substance abuse treatment should be facilitated by recent advances in behavioral science, pharmacology, neurobiology and medicinal chemistry.
药物滥用是一个重大的公共卫生问题，静脉注射药物滥用与艾滋病之间的关系凸显了对更有效治疗药物的需求。药物自我给药的动物模型有助于系统地评估新的治疗药物并预测临床疗效。本综述总结了治疗可卡因和阿片类药物滥用药物的临床前评估现状。描述了基本的药物自我给药方法以及实验设计和结果标准的原理。对多巴胺或阿片受体激动剂和拮抗剂以及临床上用于其他适应症的药物对药物自我给药的影响的研究进行了严格审查。在可能的情况下，讨论了药物滥用治疗药物临床研究和临床前研究之间的一致性程度。我们得出结论，药物自我给药模型对于药物疗效的临床前评估很有价值，并且我们推荐了一些策略来进一步改进评估程序。行为科学、药理学、神经生物学和药物化学的最新进展应有助于发现更有效的药物滥用治疗药物。
