Reducing Smoking Cue Reactivity and Behavior via a Retrieval-Extinction Mechanism

描述（由申请人提供）：在先前学习中涉及的线索的呈现可以引发对学习的记忆的检索。恢复的记忆在重新整合回长期存储之前是不稳定的。虽然不稳定，但记忆可以被改变，使得先前由记忆支持的行为被显著改变或根除。尼古丁成瘾是多因素决定的，但吸烟行为的启动和维持中的一个主要病因因素是对吸烟相关学习的记忆，其作为线索之间频繁配对的结果而发展（例如，香烟的视觉和气味）和尼古丁奖励。暴露于这些条件暗示所引发的渴望和其他反应对持续戒烟构成了重大威胁。线索暴露疗法，涉及在没有尼古丁奖励的情况下重复呈现吸烟线索，被开发用于消除线索引起的渴望和反应。随着研究表明，随着时间的推移或发生吸烟失误，熄灭的反应往往会重新出现，对这种疗法的热情减弱。这项探索性研究是根据最近的《科学》杂志发表的一篇文章进行的，该杂志报道了一种新的提取-消退干预对脱毒海洛因成瘾者渴望线索反应的影响。恢复-灭绝干预包括两个方面 会议中，简短的海洛因线索介绍，旨在引起检索，紧随其后的是长期的海洛因线索暴露的时间。值得注意的是，这种短暂的干预导致海洛因渴望和线索反应的显着减少，并持续6个月。对这些发现的一种解释是，短暂的“提取”线索暴露引发了再巩固， 从而打开了一个机会之窗，在这个窗口中，长时间的线索暴露可以用信息更新记忆，这将导致对海洛因线索的反应减弱。鉴于这些初步的和令人印象深刻的发现，我们建议检查两个会议的检索灭绝培训的吸烟者谁正在戒烟尝试的影响。将启动检索 简短（5分钟）视频与吸烟相关的内容和灭绝将包括延长（1小时）暴露在吸烟的暗示下。对照组接受相同的治疗，除了检索视频将有非吸烟/中性的内容将用于证明检索是检索-消退训练的一个关键特征。将在训练后1天、2周和4周评估训练对吸烟渴望和线索反应的影响。还将初步评估培训对吸烟指数的影响。预计这种训练的吸烟线索检索特征将导致对吸烟线索的渴望和反应性的显著和持久的降低，并对吸烟产生有利的影响。这项研究的积极发现可能会导致一种安全有效的行为干预，帮助吸烟者克服由线索引发的渴望和反应所造成的戒烟威胁，从而减轻这种最昂贵的成瘾对社会造成的负担。此外，这种治疗方法可以修改，以解决对其他滥用物质的成瘾问题。

DESCRIPTION (provided by applicant): Presentation of cues involved in prior learning can elicit retrieval of memory for the learning. Retrieved memories are unstable before they are reconsolidated back into long-term storage. While unstable, the memories can be altered such that behaviors previously supported by the memories are significantly altered or eradicated. Nicotine addiction is multi-determined but one major etiological factor in the initiation and maintenance of smoking behavior is memory for smoking-related learning that develops as a consequence of frequent pairings between cues (e.g., sight and smell of cigarettes) and nicotine reward. The craving and other reactions that are elicited by exposure to these conditioned cues represent a significant threat to sustained cessation. Cue exposure therapy, which involves the repeated presentation of smoking cues in the absence of nicotine reward, was developed to extinguish cue-elicited craving and reactivity. Enthusiasm for this therapy waned as research revealed that extinguished responses would often reemerge with passage of time or if a smoking lapse occurred. The proposed exploratory study developed out of a recent Science publication that reported on the effects of a novel retrieval-extinction intervention on craving an cue reactivity in detoxified heroin addicts. The retrieval-extinction intervention consisted of two sessions in which brief heroin cue presentations, designed to elicit retrieval, were followed closely in time by protracted heroin cue exposure. Remarkably, this brief intervention led to significant reductions in heroin craving and cue reactivity that were sustained for 6-months. One explanation for these finding is that the brief 'retrieval' cue exposure initiated reconsolidation, thereby opening a window of opportunity in which protracted cue exposure could update the memories with information that would lead to dampened responsiveness to heroin cues. Given these initial and impressive findings, we propose to examine the effects of two sessions of retrieval-extinction training in smokers who are making a quit attempt. Retrieval will be initiated by a brief (5-min.) video with smoking-related content and the extinction will consist of protracted (1 hr.) exposure to smoking cues. A control group receiving the same treatment except that the retrieval video will have nonsmoking/neutral content will serve to demonstrate that retrieval is a key feature of retrieval-extinction training. Effects of the training on smokin craving and cue reactivity will be assessed 1-day, 2-weeks and 4-weeks post-training. The effects of the training on indices of smoking will also be preliminarily assessed. It is expected that the smoking-cue retrieval feature of this training will result in significant and enduring reductions in craving and reactivity to smoking cues and have a favorable impact on smoking. Positive findings from this study could lead to a safe and effective behavioral intervention that will help smokers overcome the threat to cessation posed by cue-elicited craving and reactivity, and thereby reduce the burden levied against society by this most costly addiction. Additionally, this treatment could be modified to address addiction to other substances of abuse.