Drug self-administration has been regarded as a gold-standard preclinical model of addiction and substance-use disorder (SUD). However, investigators are becoming increasingly aware, that certain aspects of addiction or SUDs experienced by humans are not accurately captured in our preclinical self-administration models. The current review will focus on two such aspects of current preclinical drug self-administration models: 1) Predictable vs. unpredictable drug access in terms of the time and effort put into obtaining drugs (i.e., response requirement) and drug quality (i.e., amount) and 2) rich vs. lean access to drugs. Some behavioral and neurobiological mechanisms that could contribute to excessive allocation of behavior toward drug-seeking and drug-taking at the expense of engaging in nondrug-related activities are discussed, and some directions for future research are identified. Based on the experiments reviewed, lean and unpredictable drug access could worsen drug-seeking and drug-taking behavior in individuals with SUDs. Once more fully explored, this area of research will help determine whether and how unpredictable and lean cost requirements affect drug self-administration in preclinical laboratory studies with nonhuman subjects and will help determine whether incorporating these conditions in current self-administration models will increase their predictive validity.

中文翻译：

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作为药物自我给药调节剂的不可预测性：与物质使用障碍的相关性

药物自我给药已被视为成瘾和物质使用障碍 (SUD) 的黄金标准临床前模型。然而，研究人员越来越意识到，人类经历的成瘾或 SUD 的某些方面并没有在我们的临床前自我管理模型中准确捕捉到。当前的审查将集中在当前临床前药物自我给药模型的两个这样的方面：1) 就获得药物所花费的时间和精力（即反应要求）和药物质量（即数量）而言，可预测与不可预测的药物获取) 和 2) 富人与瘦人获得药物的机会。讨论了一些行为和神经生物学机制，这些机制可能以牺牲从事与毒品无关的活动为代价，导致过度分配行为到寻求毒品和吸毒上，并确定了未来研究的一些方向。根据审查的实验，精益和不可预测的药物获取可能会恶化 SUD 患者的寻药和吸毒行为。一旦得到更充分的探索，这一研究领域将有助于确定不可预测和精益成本要求是否以及如何影响非人类受试者的临床前实验室研究中的药物自我给药，并将有助于确定将这些条件纳入当前的自我给药模型是否会增加其预测性有效性。