Extinction in Smokers: Renewal and Spontaneous Recovery

当吸烟者面对之前与吸烟行为成对的线索时，这些线索会触发被认为是激励或调解药物使用的反应。这一观察结果使研究人员考虑了使用基本的动物灭绝方法来减少药物线索对人类的关联影响的潜在治疗益处。然而，事实证明，这种线索暴露疗法对上瘾的效果不如预期。它们疗效有限的一个关键原因可能是人类研究人员没有利用当代动物 研究提出了新的思考灭绝的方法，学习并通过防范威胁它的特定现象来加强它。使用吸烟作为药物使用行为的模型，RFA#MH-04-005的这份R21申请书中提出的研究将检查两个这样的对灭绝学习的威胁，即更新，即在灭绝训练后在新的环境中再次遇到熄灭的线索时，重新对其做出反应，以及自发恢复，当允许在熄灭和重新暴露于线索之间经过一段时间时发生的。拟议工作的直接目标是确定 无论是间隔呈现还是集中呈现线索，都会导致显著吸烟线索在会话中更完全地消失(研究1)。使用研究1中确定的最优消光计划，第二个目标是通过让吸烟者创建个人图画吸烟情景-将其带入实验室-来检查吸烟者的情景依赖更新效果。更新研究将确定，正如动物研究所证明的那样，增加灭绝过程中存在的上下文数量(研究2)或将灭绝提醒与灭绝训练和重新测试(研究3A)配对是否会减弱更新效应。最后一项研究将检查灭绝提醒是否也会削弱自发恢复(研究3B)。这条线路的长期目标是 研究的重点将是创造更有效的技术来消除对人类显著药物线索的条件性反应，目的是加强基于灭绝的药物成瘾治疗。此外，这里提出的实验将为有关动物尼古丁自我给药的临床前研究提供信息，以更接近反映人类线索消退研究中遇到的问题的方式接近药物消退。

When a smoker confronts cues previously paired with smoking behavior, those cues trigger responses that are presumed to motivate or mediate drug use. This observation has led researchers to consider the potential therapeutic benefit of diminishing the associative impact of drug cues in humans using basic animal extinction methods. However, such cue-exposure treatments for addiction have proven less effective than anticipated. A key reason for their limited efficacy might be that human researchers have not exploited contemporary animal research that suggest new ways of thinking about extinction learning and strengthening it by guarding against specific phenomena that threaten it. Using smoking as the model drug-use behavior, the studies proposed in this R21 application for RFA #MH-04-005 will examine two such threats to extinction learning, namely renewal, which involves renewed responding to an extinguished cue when it is re-encountered in a new context after extinction training, and spontaneous recovery, which occurs when time is allowed to pass between extinction and re-exposure to a cue. The immediate objective of the proposed work is to determine whether spaced or massed presentation of cues leads to more complete within-session extinction of a salient smoking cue (Study 1). Using the optimal extinction schedule determined in Study 1, the second aim is to examine context-dependent renewal effects in human smokers by having them create personal pictorial smoking-contexts to bring into the lab. Renewal studies will determine if, as has been demonstrated in animal studies, increasing the number of contexts present during extinction (Study 2) or pairing an extinction reminder with extinction training and re-test (Study 3A) attenuates renewal effects. A final study will examine if an extinction reminder can also attenuate spontaneous recovery (Study 3B). The long-term goal of this line of research will be to create more efficacious techniques for extinguishing conditioned responding to salient drug cues in humans for the purpose of enhancing extinction-based treatments for drug addiction. Moreover, the experiments proposed here will inform pre-clinical research on nicotine self-administration in animals with regard to approaching drug-extinction in ways that more closely reflect the problems encountered in human cue-extinction research.