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使用临床前药物与食物选择程序评估可卡因成瘾候选药物

Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

作者信息

Banks Matthew L, Hutsell Blake A, Schwienteck Kathryn L, Negus S Stevens

机构信息

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA ; Institute for Drug and Alcohol Abuse Studies, Virginia Commonwealth University, Richmond, VA, USA.

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.

出版信息

Curr Treat Options Psychiatry. 2015 Jun;2(2):136-150. doi: 10.1007/s40501-015-0042-9.

Abstract

Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to drug-maintained behaviors, but also to promote a of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940's, and during the last 10-15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser -amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

摘要

药物成瘾是一种疾病,表现为在获取和使用成瘾物质方面行为分配不当,而偏离了其他能产生更具适应性强化作用的行为(如锻炼、工作、家庭和社会关系)。治疗药物成瘾的目标不仅是戒除药物维持的行为,还包括促进行为转向替代性的、非药物性强化物。同时提供药物强化物和替代性非药物强化物以供选择的实验程序,为评估药物对药物选择和行为分配的影响提供了一种研究工具。选择程序目前是人类实验室药物研发研究的标准方法。自20世纪40年代初以来,临床前选择程序就已用于生物医学研究,在过去10至15年里,其用于评估治疗药物成瘾药物的情况有所增加。我们在此提出,在临床前和临床研究中并行使用选择程序将有助于开展治疗可卡因成瘾药物研发的转化研究。为支持这一观点,文献综述表明,候选药物在非人类灵长类动物和啮齿动物中改变可卡因选择的临床前有效性与这些药物在人类实验室研究中改变可卡因选择或在可卡因使用障碍患者中改变可卡因滥用指标的临床有效性之间存在很强的一致性。在临床前选择研究中,关于药物有效性的最有力证据是在使用单胺释放剂——苯丙胺维持给药的情况下获得的,苯丙胺是一种用于可卡因使用的候选激动剂药物,类似于使用美沙酮治疗海洛因滥用或尼古丁制剂治疗烟草依赖。

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