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

针对尼古丁成瘾的基础记忆过程：一项减少烟瘾的检索-消退干预的转化临床神经科学研究

• 批准号: 10133030
• 负责人: Michael E Saladin
• 金额: $ 53.86万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10133030
• 关键词: Abstinence; Acute; Aftercare; Amygdaloid structure; Anterior; Anxiety Disorders; Attenuated; Back; Behavior; Behavior Therapy; Brain; Brain imaging; Cigarette Smoker; Clinical; Control Groups; Corpus striatum structure; Cues; Development; Dorsal; Dose; Drug usage; Elements; Exposure to; Extinction (Psychology); Foundations; Functional Magnetic Resonance Imaging; Funding; Goals; Heroin; Hippocampus (Brain); Impairment; Inpatients; Intervention; Laboratories; Lead; Learning; Level of Evidence; Long-Term Effects; Medial; Memory; Methods; Monitor; National Institute of Drug Abuse; Neurosciences; Nicotine; Nicotine Dependence; Outcome; Participant; Pattern; Pharmaceutical Preparations; Phase; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Psychiatry; Publishing; Reaction; Relapse; Reporting; Research; Research Personnel; Rest; Retrieval; Rewards; Science; Signal Transduction; Smoker; Smoking; Smoking Behavior; Societies; Substance Use Disorder; Suggestion; Testing; Training; Treatment outcome; Ventral Striatum; Writing; addiction; base; blood oxygenation level dependent response; brief intervention; cigarette smoke; comorbidity; cost; craving; cue reactivity; design; drug seeking behavior; follow-up; heroin use; imaging modality; improved; indexing; interest; intervention effect; memory process; memory retrieval; nicotine patch; novel; post intervention; response; smoking cessation; smoking cue; therapy design; translational study; treatment effect; treatment group; treatment optimization; trend

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.

项目总结：我们最近发表了一项由nida资助的简短行为研究的结果