Department of Psychiatry, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
Center for Neuroscience, University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA, 15213, USA.
Cell Mol Life Sci. 2020 Oct;77(19):3745-3768. doi: 10.1007/s00018-020-03498-8. Epub 2020 Mar 14.
Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can lead to relapse. Understanding the neural underpinnings of how these associations are formed and maintained will inform future advances in treatment practices. A large body of research has expanded our knowledge of how associative memories are acquired and consolidated, how they are updated through reactivation and reconsolidation, and how competing extinction memories are formed. This review will focus on the vast literature examining the mechanisms of cocaine Pavlovian associative memories with an emphasis on the molecular memory mechanisms and circuits involved in the consolidation, reconsolidation, and extinction of these memories. Additional research elucidating the specific signaling pathways, mechanisms of synaptic plasticity, and epigenetic regulation of gene expression in the circuits involved in associative learning will reveal more distinctions between consolidation, reconsolidation, and extinction learning that can be applied to the treatment of substance use disorders.
复发的风险是物质使用障碍治疗中的一个主要挑战。几种类型的学习和记忆机制与物质使用有关，并与复发有关。药物的作用与周围环境刺激之间形成了联想记忆，在戒断期间暴露于这些刺激会引起压力并引发药物渴望，从而导致复发。了解这些关联是如何形成和维持的神经基础将为未来的治疗实践提供信息。大量研究扩展了我们对联想记忆是如何获得和巩固的、它们如何通过重新激活和再巩固进行更新的、以及如何形成竞争性的遗忘记忆的理解。这篇综述将重点介绍大量研究可卡因 Pavlovian 联想记忆的机制的文献，强调涉及这些记忆的巩固、再巩固和遗忘的分子记忆机制和回路。进一步的研究阐明了涉及联想学习的回路中特定信号通路、突触可塑性机制和基因表达的表观遗传调控，将揭示巩固、再巩固和遗忘学习之间的更多区别，这些区别可应用于物质使用障碍的治疗。
