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Nonhuman animal models of substance use disorders: Translational value and utility to basic science.
Drug and Alcohol Dependence ( IF 3.9 ) Pub Date : 2019-11-21 , DOI: 10.1016/j.drugalcdep.2019.107733
Mark A Smith 1
Affiliation  

BACKGROUND The National Institute on Drug Abuse (NIDA) recently released a Request for Information (RFI) soliciting comments on nonhuman animal models of substance use disorders (SUD). METHODS A literature review was performed to address the four topics outlined in the RFI and one topic inspired by the RFI: (1) animal models that best recapitulate SUD, (2) animal models that best balance the trade-offs between resources and ecological validity, (3) animal models whose translational value are frequently misrepresented or overrepresented by the scientific community, (4) aspects of SUD that are not currently being modeled in animals, and (5) animal models that are optimal for examining the basic mechanisms by which drugs produce their abuse-related effects. RESULTS Models that employ response-contingent drug administration, use complex schedules of reinforcement, measure behaviors that mimic the distinguishing features of SUD, and use animals that are phylogenetically similar to humans have the greatest translational value. Models that produce stable and reproducible baselines of behavior, lessen the number of uncontrolled variables, and minimize the influence of extraneous factors are best at examining basic mechanisms contributing to drug reward and reinforcement. CONCLUSIONS Nonhuman animal models of SUD have undergone significant refinements to increase their utility for basic science and translational value for SUD. The existing literature describes numerous examples of how these models may best be utilized to answer mechanistic questions of drug reward and identify potential therapeutic interventions for SUD. Progress in the field could be accelerated by further collaborations between researchers using animals versus humans.

中文翻译:

物质使用失调的非人类动物模型:转化价值和对基础科学的实用性。

背景技术美国国家药物滥用研究所(NIDA)最近发布了一项信息请求(RFI),以征询有关药物滥用障碍(SUD)的非人类动物模型的评论。方法进行了文献综述,以解决RFI中概述的四个主题和受RFI启发的一个主题:(1)最能概括SUD的动物模型,(2)最能平衡资源与生态有效性之间权衡的动物模型。 ,(3)翻译价值经常被科学界错误地代表或过度代表的动物模型,(4)目前尚未在动物中建模的SUD方面,以及(5)最适合用来检查其基本机制的动物模型药物会产生与滥用相关的效果。结果采用响应性或偶然药物管理的模型,使用复杂的加固时间表,测量模仿SUD区别特征的行为,并使用与人类在系统发育上相似的动物具有最大的翻译价值。产生稳定且可重现的行为基准,减少不受控制的变量的数量以及最小化外部因素的影响的模型最适合检查有助于药物奖励和强化的基本机制。结论SUD的非人类动物模型已经进行了重大改进,以增加其在SUD的基础科学和转化价值中的应用。现有文献描述了如何最好地利用这些模型来回答药物奖励机制问题并确定SUD潜在治疗干预措施的众多例子。
更新日期:2019-11-21
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