Moeller Scott J, Stoops William W
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Department of Behavioral Science and Center on Drug and Alcohol Research, University of Kentucky College of Medicine, Lexington, KY, United States; Department of Psychiatry, University of Kentucky College of Medicine, Lexington, KY, United States; Department of Psychology, University of Kentucky College of Arts and Sciences, Lexington, KY, United States.
Pharmacol Biochem Behav. 2015 Nov;138:133-41. doi: 10.1016/j.pbb.2015.09.020. Epub 2015 Sep 30.
Individuals with cocaine use disorder chronically self-administer cocaine to the detriment of other rewarding activities, a phenomenon best modeled in laboratory drug-choice procedures. These procedures can evaluate the reinforcing effects of drugs versus comparably valuable alternatives under multiple behavioral arrangements and schedules of reinforcement. However, assessing drug-choice in treatment-seeking or abstaining humans poses unique challenges: for ethical reasons, these populations typically cannot receive active drugs during research studies. Researchers have thus needed to rely on alternative approaches that approximate drug-choice behavior or assess more general forms of decision-making, but whether these alternatives have relevance to real-world drug-taking that can inform clinical trials is not well-understood. In this mini-review, we (A) summarize several important modulatory variables that influence cocaine choice in nonhuman animals and non-treatment seeking humans; (B) discuss some of the ethical considerations that could arise if treatment-seekers are enrolled in drug-choice studies; (C) consider the efficacy of alternative procedures, including non-drug-related decision-making and 'simulated' drug-choice (a choice is made, but no drug is administered) to approximate drug choice; and (D) suggest opportunities for new translational work to bridge the current divide between preclinical and clinical research.
患有可卡因使用障碍的个体长期自行服用可卡因,从而损害了其他有回报的活动,这一现象在实验室药物选择程序中得到了最佳模拟。这些程序可以在多种行为安排和强化时间表下评估药物与同等有价值的替代物的强化效果。然而,在寻求治疗或已戒除的人群中评估药物选择带来了独特的挑战:出于伦理原因,这些人群在研究期间通常不能接受活性药物。因此,研究人员需要依靠近似药物选择行为或评估更一般形式决策的替代方法,但这些替代方法是否与可指导临床试验的现实世界药物服用相关,目前还不太清楚。在本综述中,我们(A)总结了几个影响非人类动物和未寻求治疗的人类中可卡因选择的重要调节变量;(B)讨论了如果寻求治疗者参加药物选择研究可能出现的一些伦理考量;(C)考虑替代程序的有效性,包括与药物无关的决策和“模拟”药物选择(做出选择,但不给予药物)以近似药物选择;以及(D)提出新的转化研究工作机会,以弥合当前临床前研究和临床研究之间的差距。