Relapse to drug use during abstinence is a defining feature of addiction. During the last several decades, this clinical scenario has been studied at the preclinical level using classic relapse/reinstatement models in which drug seeking is assessed after experimenter-imposed home-cage forced abstinence or extinction of the drug-reinforced responding in the self-administration chambers. To date, however, results from studies using rat relapse/reinstatement models have yet to result in Food and Drug Administration–approved medications for relapse prevention. The reasons for this state of affairs are complex and multifaceted, but one potential reason is that, in humans, abstinence is often self-imposed or voluntary and occurs either because the negative consequences of drug use outweigh the drug’s rewarding effects or because of the availability of nondrug alternative rewards that are chosen over the drug. Based on these considerations, we and others have recently developed rat models of relapse after voluntary abstinence, achieved either by introducing adverse consequences to drug taking (punishment) or seeking (electric barrier) or by providing mutually exclusive choices between the self-administered drug and nondrug rewards (palatable food or social interaction). In this review, we provide an overview of these translationally relevant relapse models and discuss recent neuropharmacological findings from studies using these models. We also discuss sex as a biological variable, future directions, and clinical implications of results from relapse studies using voluntary abstinence models. Our main conclusion is that the neuropharmacological mechanisms controlling relapse to drug seeking after voluntary abstinence are often different from the mechanisms controlling relapse after home-cage forced abstinence or reinstatement after extinction.

中文翻译：

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自愿戒断后药物复发和渴望的动物模型：综述


戒断期间再次吸毒是成瘾的一个明显特征。在过去的几十年中，这种临床情况已经在临床前水平上使用经典的复发/恢复模型进行了研究，其中在实验者强制禁欲或自我给药中药物强化反应消失后评估药物寻求室。然而，迄今为止，使用大鼠复发/恢复模型的研究结果尚未导致美国食品和药物管理局批准用于预防复发的药物。造成这种状况的原因是复杂且多方面的，但一个潜在的原因是，对于人类来说，戒断往往是自我强加的或自愿的，并且发生的原因要么是因为吸毒的负面后果超过了药物的奖励作用，要么是因为药物的可用性选择非药物替代奖励而不是药物。基于这些考虑，我们和其他人最近开发了自愿戒毒后复发的大鼠模型，通过对吸毒（惩罚）或寻求（电屏障）引入不良后果或通过在自我给药和戒毒之间提供相互排斥的选择来实现。非药物奖励（可口的食物或社交互动）。在这篇综述中，我们概述了这些翻译相关的复发模型，并讨论了使用这些模型的研究的最新神经药理学发现。我们还讨论了性别作为一个生物学变量、未来的方向以及使用自愿戒断模型进行的复发研究结果的临床意义。 我们的主要结论是，控制自愿戒断后寻求药物复发的神经药理学机制通常不同于控制在家笼强制戒断或灭绝后恢复后复发的机制。