The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

大多数吸烟者即使在成功戒烟后也会复发，因为在意外地重新暴露于与吸烟相关的线索后对吸烟的渴望。这种有条件的渴望是由经常经历和顽固地抵抗治疗的奖励记忆介导的。重新整合理论认为，整合良好的记忆在检索后会变得不稳定，这一过程使记忆变得不稳定并容易受到遗忘干预。这项研究测试了检索再巩固程序，以减少吸烟者对尼古丁的渴望。在这项研究中，52 名男性吸烟者接受了单剂量的普萘洛尔（n  = 27）或安慰剂（n = 25）在重新激活尼古丁相关记忆以损害重新巩固过程之前。对吸烟的渴望和响应吸烟相关线索的神经活动是主要结果。在记忆再巩固过程中进行功能性磁共振成像。普萘洛尔对再巩固的破坏降低了对吸烟的渴望。在重新巩固操作后，普萘洛尔组中央后回对吸烟相关线索的反应性也降低。在普萘洛尔组的记忆重建过程中，海马和纹状体之间的功能连接性更高。此外，海马和纹状体之间耦合的增加与普萘洛尔组再巩固操作后渴望的减少呈正相关。在记忆重新激活之前服用普萘洛尔，通过调节参与记忆和奖励处理的大脑区域，破坏了吸烟者吸烟相关记忆的重新巩固。这些发现证明了去甲肾上腺素能调节人类记忆的重新巩固，并表明辅助普萘洛尔可以促进尼古丁依赖的治疗。本研究已在 ClinicalTrials.gov 预注册（注册号 ChiCTR1900024412）。这些发现证明了去甲肾上腺素能调节人类记忆的重新巩固，并表明辅助普萘洛尔可以促进尼古丁依赖的治疗。本研究已在 ClinicalTrials.gov 预注册（注册号 ChiCTR1900024412）。这些发现证明了去甲肾上腺素能调节人类记忆的重新巩固，并表明辅助普萘洛尔可以促进尼古丁依赖的治疗。本研究已在 ClinicalTrials.gov 预注册（注册号 ChiCTR1900024412）。