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.

项目摘要/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有效 治疗成瘾。研究表明，这些药物的给药可以减少对 通过关联学习范式与滥用药物相关的环境（即条件地点 偏爱）并防止扩展后恢复原状。虽然这些神经机制 在啮齿动物模型中仔细检查了效果，很少研究神经行为 普萘洛尔对人类对药物使用刺激的反应的影响。我们的实验室最近的一项研究表明 暴露于个人药物使用环境的图像激活了涉及的相同大脑区域 啮齿动物模型中条件位置偏好的表达。这个成像 - 科学轨道奖 研究过渡（I/Start）赠款将扩展这项工作，以检查普萘洛尔对神经和 人类吸烟者对药物使用环境的行为反应。这个项目的总体目标是 阐明普萘洛尔可能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。四十名成年吸烟者会识别和 他们与吸烟和环境相关的照相环境 我们已经开发和验证的过程。然后，他们将被随机分配以接收 丙醇（40毫克）或安慰剂，直到进行功能性磁共振成像之前 （fMRI）扫描。在扫描过程中，他们将查看他们以前的个性化吸烟环境的图像 照片以及标准的吸烟环境和近端吸烟提示（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，以检测他们的抵抗能力 吸烟以换取货币激励措施，同时接触个性化吸烟环境 继续。我们假设普萘洛尔会响应个人吸烟而减轻大脑的激活 先前研究中确定的几个目标大脑区域的环境，减少激活的协变 在这些地区（即功能连接），并增加了抵抗吸烟以换取的意愿 货币激励措施。其他探索性分析将检查神经之间的关系 激活/连通性和吸烟/行为。 I/Start Grant的结果将为A提供支持 随后的R01申请研究了普萘洛尔和类似药物的神经机制 大规模试验的背景。根据这项研究，具有强大的翻译潜力。它将提供 关于β肾上腺素药物对反应的影响的神经基础的有价值的信息 毒品使用环境及其与吸烟行为的关系。它还将为发展和研究 新颖的和已建立的药物吸烟和其他成瘾的药物疗法。