Neurobehavioral substrates of propranolol's effects on drug cue reactivity

普萘洛尔对药物提示反应性影响的神经行为底物

• 批准号: 9387245
• 负责人: Jason Anthony Oliver
• 金额: $ 23.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387245
• 关键词: Abstinence; Adrenergic Agents; Adrenergic Antagonists; Adrenergic beta-Antagonists; Adult; Affect; Amygdaloid structure; Animal Model; Animals; Area; Attenuated; Award; Behavior; Behavioral; Behavioral Mechanisms; Biological Assay; Brain; Brain region; Cigarette Smoker; Clinical; Cues; Data; Development; Dorsal; Drug usage; Emotions; Environment; Exposure to; Extinction (Psychology); Functional Magnetic Resonance Imaging; Goals; Grant; Hippocampus (Brain); Human; Image; Incentives; Individual; Insula of Reil; Laboratories; Laboratory Study; Literature; Measures; Medial; Mediating; Memory; Methods; Motivation; Neurobiology; Nicotine Dependence; Participant; Patient Self-Report; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Placebos; Play; Pre-Clinical Model; Prefrontal Cortex; Procedures; Propranolol; Publishing; Randomized; Relapse; Research; Research Personnel; Retrieval; Rodent; Rodent Model; Role; Scanning; Science; Sex Characteristics; Smoker; Smoking; Smoking Behavior; Specificity; Stimulus; System; Time; Translations; Work; addiction; analog; base; behavioral outcome; behavioral response; brain behavior; cigarette smoking; classical conditioning; cue reactivity; drug of abuse; indexing; memory retrieval; neurobehavioral; neuroimaging; neuromechanism; non-smoking; novel; pre-clinical; preference; public health relevance; relating to nervous system; response; smoking cessation; smoking relapse; willingness

PROJECT SUMMARY/ABSTRACT A growing body of pre-clinical literature suggests beta-adrenergic antagonist medications may be effective for treating addiction. Studies show that administration of these medications can reduce preference for environments associated with drugs of abuse via associative learning paradigms (i.e. conditioned place preference) and protect against reinstatement following extinction. Although the neural mechanisms of these effects have been carefully examined in rodent models, very little research has examined the neurobehavioral effects of propranolol on responses to drug use stimuli in humans. A recent study in our laboratory indicated that exposure to images of personal drug-use contexts activates the same brain regions involved in the expression of conditioned place preference in rodent models. This Imaging – Science Track Award for Research Transition (I/START) grant will extend that work to examine the effects of propranolol on neural and behavioral responses to drug-use contexts in human smokers. The overarching goal of this project is to elucidate the brain mechanisms through which propranolol may exert an effect on human smoking behavior and to obtain preliminary data regarding its potential clinical use. Forty adult smokers will identify and photograph environments they associate with smoking and environments they associate with abstinence using a procedure we have developed and validated. They will then be randomly assigned to receive either propranolol (40-mg) or placebo immediately prior to undergoing a functional magnetic resonance imaging (fMRI) scan. During the scan, they will view images of the personalized smoking environments they previously photographed, as well as standard smoking environments and proximal smoking cues (e.g. lighters, ashtrays). Immediately following the scan, participants will complete a laboratory task that assays their ability to resist smoking in exchange for monetary incentives while exposure to personalized smoking environments continues. We hypothesize that propranolol will attenuate brain activations in response to personal smoking environments across several target brain regions identified in prior research, reduce covariation of activations across these regions (i.e. functional connectivity) and increase willingness to resist smoking in exchange for monetary incentives. Additional exploratory analyses will examine the relationship between neural activation/connectivity and smoking urge/behavior. Results of this I/START grant will provide support for a subsequent R01 application investigating the neural mechanisms of propranolol and similar medications in the context of larger-scale trials. Accordingly, this research has strong potential for translation. It will provide valuable information on the neural underpinnings of the effects of beta adrenergic medications on responses to drug-use contexts and their relationship with smoking behavior. It will also inform the development and study of both novel and established pharmacological treatments for cigarette smoking and other addictions.

项目概要/摘要 越来越多的临床前文献表明，β-肾上腺素能拮抗剂药物可能对以下疾病有效： 研究表明，服用这些药物可以减少对成瘾的偏好。 通过联想学习范式（即条件性场所）与滥用药物相关的环境 偏好）并防止灭绝后的恢复，尽管这些神经机制。 已经在啮齿动物模型中仔细检查了影响，但很少有研究检查神经行为 我们实验室最近的一项研究表明普萘洛尔对人类药物使用刺激反应的影响。 暴露于个人吸毒环境的图像会激活参与吸毒的相同大脑区域 啮齿类动物模型中条件性位置偏好的表达——该成像——科学赛道奖。 研究过渡 (I/START) 资助将扩大这项工作，以检查普萘洛尔对神经和神经系统的影响 人类吸烟者对吸毒环境的行为反应 该项目的总体目标是 阐明普萘洛尔对人类吸烟行为产生影响的大脑机制 并获得有关其潜在临床用途的初步数据将识别和确定四十名成年吸烟者。 使用照片拍摄与吸烟相关的环境以及与戒烟相关的环境 我们开发并验证了一个程序，然后他们将被随机分配接受其中一个。 在进行功能性磁共振成像之前立即服用普萘洛尔（40 毫克）或安慰剂 (fMRI) 扫描期间，他们将查看之前个性化吸烟环境的图像。 拍摄照片，以及标准吸烟环境和邻近吸烟线索（例如打火机、烟灰缸）。 扫描后，参与者将立即完成一项实验室任务，分析他们的抵抗能力 在暴露于个性化吸烟环境的同时吸烟以换取金钱奖励 我们发现普萘洛尔会减弱大脑对个人吸烟的反应。 先前研究中确定的跨多个目标大脑区域的环境，减少激活的协变 跨这些区域（即功能连接）并提高抵制吸烟的意愿以换取 额外的探索性分析将检查神经元之间的关系。 该 I/START 资助的结果将为一项活动提供支持。 随后的 R01 应用研究了普萘洛尔和类似药物的神经机制 因此，这项研究具有巨大的转化潜力。 关于β肾上腺素能药物对反应的神经基础的有价值的信息 它还将为药物使用环境及其与吸烟行为的关系提供信息。 针对吸烟和其他成瘾问题的新颖和成熟的药物治疗方法。