Targeting Foundational Memory Processes in Nicotine Addiction: A Translational Clinical Neuroscience Study of a Retrieval-Extinction Intervention to Reduce Craving & Smoking Behavior

项目概要：我们最近发表了一项由NIDA资助的研究结果， 治疗，旨在减少吸烟者遇到的麻烦渴望，当他们试图 戒烟这种干预是基于越来越多的神经科学研究表明，记忆 可以通过呈现学习中涉及的线索来检索。一旦恢复， 记忆会进入一个短暂的脆弱期，在此期间，它们可以被修改，但在此之后， 重新巩固（重新稳定）为长期储存。这种现象的治疗潜力是 最初在《科学》杂志的一份报告中得到证实， 与海洛因使用相关的记忆，以促使海洛因使用记忆进入脆弱状态。一旦 当记忆处于这种状态时，海洛因成瘾者接受了灭绝训练，包括长时间暴露于 海洛因相关线索有人认为，灭绝会改变记忆，这样的线索就不会 不再与海洛因管理和奖励有关。值得注意的是，在仅仅两次检索后- 灭绝训练（RET），研究人员发现，对海洛因线索的渴望实质上是 治疗后6个月内减少。观察到的这种效果与对照组相比， 涉及非海洛因线索的检索，然后是灭绝。这些令人印象深刻的初步发现让我们复制了 并将研究扩展到吸烟者。在我们的研究中，一组吸烟者接受了两次RET 而对照组接受相同的训练，除了检索包括简短的 暴露于中性的，与吸烟无关的线索。对熟悉和新颖的吸烟线索的渴望和其他反应 在干预后24小时、2周和1个月进行的测试中进行评估;吸烟行为 还在1个月的随访中进行了评估。值得注意的是，在1个月的随访中， 接受R-E训练的组与对照组相比，新的吸烟线索显著降低。更引人注目 RET组与对照组相比，每天吸烟的数量减少了25%。[Also的 显著性提示性证据表明，相对于对照组参与者，RET组中更多的参与者 吸烟减少60%（从治疗前水平）]。拟议项目将复制和 通过以下方式扩展这些发现：1）增加干预剂量以加强观察到的治疗效果， 2)使用脑成像方法来识别与脑损伤相关的脑活动模式。 干预和潜在的治疗结果的预测，3）增加一个对照组， 了解RET的效果，以及4）延长随访期，以更完整地记录长期- 长期的影响。这项研究的积极结果可能会导致制定一个简短，有效的 行为干预，以减轻吸烟对社会造成的负担。重要的是，这种干预 可以很容易地适应于治疗其他形式的成瘾和并发的焦虑症，如创伤后应激障碍。

PROJECT SUMMARY: We recently published results from a NIDA-funded study of a brief behavioral treatment that was designed to reduce the troublesome cravings that smokers encounter when they attempt to quit smoking. This intervention was based on a growing body of neuroscience studies showing that memories for prior learning can be retrieved by the presentation of cues involved in that learning. Once retrieved, the memories enter into a brief period of vulnerability, during which they can be modified, but after which they are reconsolidated (restabilized) back into long-term storage. The treatment potential of this phenomenon was initially demonstrated in a Science report in which inpatient heroin addicts were briefly exposed to cues associated with heroin use in order to prompt the heroin use memories into a vulnerable state. Once the memories were in this state, the heroin addicts received extinction training consisting of protracted exposure to heroin associated cues. It was argued that extinction would change the memories such that the cues would no longer be associated with heroin administration and reward. Remarkably, after just two sessions of retrieval- extinction training (RET), the investigators found that craving in response to heroin cues was substantially reduced for up to 6-months post-treatment. This effect was observed relative to a control group that received retrieval involving non-heroin cues, followed by extinction. These impressive initial findings led us to replicate and extend the study in cigarette smokers. In our study, one group of smokers received two sessions of RET with smoking cues whereas a control group received the same training except that retrieval consisted of brief exposure to neutral, smoking-unrelated cues. Craving and other reactions to familiar and novel smoking cues were assessed in test sessions performed 24-hrs, 2-weeks and 1-month after intervention; smoking behavior was also assessed over 1-month follow-up. Remarkably, at 1-month follow-up, craving to both familiar and novel smoking cues was significantly lower in the group receiving R-E training vs. control. Even more striking was the 25% reduction in the number of cigarettes smoked per day in the RET group vs. control. [Also of significance was suggestive evidence that, relative to control participants, more participants in the RET group achieved a 60% reduction in smoking (from pretreatment levels)]. The proposed project will replicate and extend these findings by 1) increasing the dose of intervention so as to bolster the observed treatment effects, 2) employing brain imaging methods to identify patterns of brain activity uniquely associated with the intervention and potentially predictive of treatment outcome, 3) adding a control group that will enhance understanding of the effects of RET, and 4) extending follow-up period to more completely document the long- term effects of RET. Positive findings from this study could lead to the development of a brief, effective behavioral intervention to reduce the burden levied against society by smoking. Importantly, this intervention could be easily adapted to treat other forms of addiction and co-occurring anxiety disorders, such as PTSD.