Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms

药物提示反应性的β-肾上腺素调节：神经和行为机制

基本信息

批准号：
10446411
负责人：
Jason Anthony Oliver
金额：
$ 48.83万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10446411
关键词：
Acute Address Adjuvant Analgesic Adjuvant Therapy Adrenergic Agents Adrenergic Antagonists Adult Amygdaloid structure Attention Attenuated Automobile Driving Award Basic Science Behavior Behavioral Behavioral Mechanisms Brain Brain region Cerebrovascular Circulation Cessation of life Cigarette Cigarette Smoker Clinical Clinical Research Crossover Design Cues Development Drug Modulation Drug Targeting Drug usage Emotional Exposure to Follow-Up Studies Future Goals Health Personnel Hippocampus (Brain)Hour Human Image Impairment Intervention Laboratories Medial Mediating Mediation Memory Methods Modeling Motivation National Institute of Drug Abuse Nicotine Withdrawal Participant Pathway interactions Pattern Perfusion Pharmaceutical Preparations Pharmacology Placebos Play Pre-Clinical Model Prefrontal Cortex Procedures Propranolol Protocols documentation Psychological reinforcement Public Health Relapse Research Research Personnel Rest Retrieval Rodent Model Role Sampling Scanning Scientist Series Shapes Smoker Smoking Smoking Behavior Smoking Cessation Intervention Stimulus System Testing Translational Research United States Withdrawal Symptom Work addiction base behavioral response beta-adrenergic receptor cerebrovascular cigarette smoking cognitive control cognitive process craving cue reactivity design drug development functional MRI scan imaging science improved neurobiological mechanism neuroimaging neuromechanism nicotine patch pill pre-clinical preclinical study preference programs relating to nervous system response smoking abstinence smoking cessation smoking cue therapy development

项目摘要

PROJECT SUMMARY/ABSTRACT More than 50% of smokers attempt to quit smoking each year, but even with intensive treatment the overwhelming majority will return to smoking within six months. Given over 480,000 deaths each year in the United States alone are directly attributable to smoking, there is a tremendous need for improved smoking cessation interventions. β-adrenergic receptor antagonists have received substantial attention as a potential treatment for addiction across both pre-clinical and clinical models. Traditional smoking cessation medications are very effective for alleviating nicotine withdrawal but much less effective at addressing the influence of environmental cues on smoking behavior. One key advantage of β-adrenergic drugs is that they target a different mechanism than established treatments, acting to directly curb the influence of these environmental cues on smoking motivation. This creates the potential for adjuvant medication interventions, whereby β- adrenergic drugs are used in combination with medications targeting nicotine withdrawal to maximize potential efficacy. A recently completed study in our laboratory supports this idea, demonstrating that acute administration of propranolol reduces cue-provoked craving, suppresses neural response to smoking stimuli (e.g. cigarettes, lighters), and alters connectivity between key brain regions shown to mediate effects in pre- clinical models. This application seeks to expand upon this work by examining the impact of β-adrenergic drugs on neural and behavioral response to smoking cues in a larger sample using a design that enables examination of the effects of a β-adrenergic antagonist alone and in combination with an established smoking cessation medication targeting nicotine withdrawal. Adult cigarette smokers (N = 80) will systematically photograph their personal smoking contexts using procedures we have developed and validated. They will then undergo four functional magnetic resonance imaging (fMRI) scans during which they will be exposed to smoking stimuli, including images of their personal smoking contexts. Prior to each scan, they will receive either: 1) Nicotine Patch + β-Adrenergic Antagonist; 2) Placebo Patch + β-Adrenergic Antagonist; 3) Nicotine Patch + Placebo Drug; and 4) Placebo Patch + Placebo Drug. Analyses will examine the effects of these medications on craving and neural activation in response to smoking cues (Aim 1), as well as neural connectivity (Aim 2). In addition, an exploratory aim will examine whether observed effects are mediated by changes in cerebrovascular perfusion or neural connectivity at rest (Exploratory Aim 3). Results from this translational project will provide valuable information on the neural underpinnings of β-adrenergic medications. It will directly inform the development of a new line of pharmacological agents for smoking cessation and provide a deeper understanding of mechanisms that can be used to help refine future intervention protocols.

项目概要/摘要每年有超过 50% 的吸烟者尝试戒烟，但即使经过强化治疗，鉴于每年有超过 480,000 人死亡，绝大多数人将在六个月内恢复吸烟。仅美国就直接归因于吸烟，因此迫切需要改善吸烟状况 β-肾上腺素能受体拮抗剂作为一种潜在的戒烟干预措施已受到广泛关注。传统戒烟药物的成瘾治疗。对于缓解尼古丁戒断非常有效，但在解决尼古丁影响方面效果较差环境因素对吸烟行为的影响 β-肾上腺素能药物的一个主要优点是它们的目标是与既定处理方法不同的机制，可直接抑制这些环境的影响这创造了辅助药物干预的潜力，从而产生β-。肾上腺素能药物与针对尼古丁戒断的药物联合使用，以最大限度地发挥潜力我们实验室最近完成的一项研究支持了这一观点，证明了这一点。服用普萘洛可减少线索引起的渴望，抑制对吸烟刺激的神经反应（例如香烟、打火机），并改变关键大脑区域之间的连接，这些区域被证明可以介导前阶段的影响。该应用旨在通过检查 β-肾上腺素能的影响来扩展这项工作。使用一种设计，在更大的样本中研究对吸烟线索的神经和行为反应的药物检查单独使用 β-肾上腺素能拮抗剂以及与既定吸烟相结合的效果针对尼古丁戒断的戒烟药物将系统地针对成年吸烟者（N = 80）。他们会使用我们开发和验证的程序拍摄他们的个人吸烟情况。然后接受四次功能磁共振成像 (fMRI) 扫描，在此期间他们将暴露于吸烟刺激，包括他们个人吸烟情况的图像，在每次扫描之前，他们都会收到。 1) 尼古丁贴片 + β-肾上腺素能拮抗剂；2) 安慰剂贴片 + β-肾上腺素能拮抗剂；3) 尼古丁贴片贴剂 + 安慰剂药物；以及 4) 安慰剂贴剂 + 安慰剂药物分析将检查这些药物的效果。药物治疗对吸烟信号的渴望和神经激活（目标 1），以及神经连接性（目标 2）此外，探索性目标将检查观察到的影响是否是由静息时脑血管灌注或神经连接的变化（探索性目标 3）。转化项目将提供有关 β-肾上腺素能药物的神经基础的有价值的信息。它将直接为戒烟和戒烟新药理制剂的开发提供信息。提供对可用于帮助完善未来干预方案的机制的更深入理解。