Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, 3052, Australia.
Psychopharmacology (Berl). 2019 Jan;236(1):439-448. doi: 10.1007/s00213-018-4929-1. Epub 2018 May 24.
Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drug-reinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies.
临床研究的结果表明，药物复发和渴望通常是由接触与药物相关的环境引起的。自 2002 年以来，实验室动物已经使用 ABA 更新模型对这种现象进行了建模。在该模型的经典版本中，在一个环境（A）中具有药物自我给药史的大鼠在另一个环境（B）中进行消退，并在暴露于原始药物相关环境（A）后重新开始（或复发）药物寻求。在 2013 年引入的模型的最新版本中，环境 A 中的实验条件与经典模型中使用的条件相同，但环境 B 中的药物强化反应受到概率惩罚的抑制。基于惩罚的 ABA 更新模型被认为类似于人类的禁欲，禁欲通常是由于避免药物使用的负面后果的愿望而引发的。我们综述的目的是讨论在两种模型中，在抑制环境 B 中的药物寻求和环境 A 中引发药物寻求复发的机制中发挥作用的相似性和差异。我们首先描述了在环境 B 中调节药物强化反应的消退和惩罚的心理机制。然后，我们总结了最近关于消退或惩罚性禁欲后环境引起的药物寻求复发的大脑机制的发现。这些发现表明，在 ABA 更新模型的两种变体中，大脑机制既有相似之处，也有不同之处。最后，我们简要讨论了临床前研究的临床意义。
