FMRI of cigarette smoking: Effects of dependence, withdrawal, and conditioned rei

吸烟的 FMRI：依赖、戒断和条件反射的影响

• 批准号: 7313230
• 负责人: KIMBERLY P LINDSEY
• 金额: $ 22.81万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-25 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7313230
• 关键词: Abstinence; Acute; Area; Behavioral; Brain; Brain imaging; Brain region; Cause of Death; Chronic; Cigarette; Clinical; Compatible; Condition; Daily; Data; Dependence; Development; Devices; Dose; Drug Kinetics; Drug effect disorder; Esthesia; Exhibits; Functional Magnetic Resonance Imaging; Hospitals; Human; Image; Imaging Techniques; Individual; Infusion procedures; Laboratories; Life; Localized; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Measures; Mediating; Meta-Analysis; Methods; Modeling; Neurobiology; Neurons; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Nicotinic Receptors; Pattern; Pharmaceutical Preparations; Physiological; Placebo Effect; Placebos; Play; Property; Protocols documentation; Psychological reinforcement; Rate; Reporting; Research; Resolution; Rewards; Role; Route; Saline; Scanning; Schedule; Sensory; Series; Sex Characteristics; Signal Transduction; Smell Perception; Smoke; Smoker; Smoking; Taste Perception; Techniques; Time; Tobacco; Tobacco smoking; Withdrawal; Withdrawal Symptom; addiction; base; blood oxygen level dependent; cigarette smoking; craving; day; density; design; hemodynamics; human subject; improved; insight; neuroimaging; nicotine abuse; nicotine replacement; paired stimuli; preclinical study; receptor; receptor density; reinforcer; research study; response; size; smoking cessation

DESCRIPTION (provided by applicant): Blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) can be used to visualize the localized hemodynamic changes in brain which occur in response to drug-induced changes in brain activation. The objective of this proposal is to use this technique to measure changes in brain activation that occur during and after smoking tobacco and placebo cigarettes. Few studies have been reported which have measured the impact of nicotine or placebo on brain activation using BOLD fMRI. None of these have used smoked cigarettes. A magnetic resonance (MR)-compatible smoking device has been developed at McLean Hospital Brain Imaging Center that can be used to allow smoking by subjects with concurrent MR imaging. Additionally, it has been repeatedly shown that conditioned reinforcers, such as the taste and smell of smoke, as well as airway sensations associated with smoking serve as powerful reinforcers in nicotine dependent individuals. The studies outlined here are designed to separate these conditioned reinforcers from the primary reinforcing effects of nicotine, and evaluate their impact on BOLD fMRI signal. OBJECTIVE: To use blood oxygen level dependent functional magnetic resonance imaging to visualize local hemodynamic changes in brain during the smoking of tobacco or placebo cigarettes and during nicotine and saline infusion. Subjective ratings of drug effect will also be measured throughout the imaging session. Experiments involving manipulations of nicotine withdrawal status and nicotine dependence state will yield data that will reveal the impact of both these factors on the acute effects of smoked or injected nicotine or placebo on both smoking-induced BOLD changes and subjective ratings of drug effect. SPECIFIC AIM 1 Evaluate the time course of changes in BOLD signal and subjective ratings of drug effect in response to smoked tobacco: Effects of abstinence and dependence. SPECIFIC AIM 2: Evaluate the time course of changes in BOLD signal and subjective ratings of placebo effect in response to smoked placebo tobacco: Effects of abstinence and dependence. SPECIFIC AIM 3: Evaluate the time course of changes in BOLD signal and subjective ratings of drug effect in response to i.v. nicotine or saline infusion in abstinent nicotine dependent smokers. RATIONALE: Previous neuroimaging studies of the effects of nicotine have used routes of administration other than smoking. Since smoking provides the most rapid onset of drug effects and since smoking is the method of nicotine administration used by smokers (often tens of times daily), a better understanding of the effects of smoked nicotine and the impact of conditioned reinforcers associated with smoking on a correlate of brain activation during smoking is crucial. The idea that withdrawal and dependence may influence this effect is supported by previous clinical and preclinical studies. Smoking is the leading preventable cause of death. Despite decades of research, there are no effective treatments for cigarette addiction. A better understanding of the effects of smoked nicotine and placebo in living human brain may provide clues to guide development of rational and efficacious treatments.

描述（由申请人提供）：血氧水平依赖性（BOLD）功能磁共振成像（fMRI）可用于可视化大脑中局部血流动力学变化，这些变化是响应药物诱导的大脑激活变化而发生的。该提案的目的是利用这种技术来测量吸食烟草和安慰剂香烟期间和之后发生的大脑激活变化。很少有研究使用 BOLD fMRI 测量尼古丁或安慰剂对大脑激活的影响。这些人都没有吸过香烟。麦克莱恩医院脑成像中心开发了一种与磁共振 (MR) 兼容的吸烟装置，可用于允许受试者在同时进行 MR 成像时吸烟。此外，一再证明，条件强化物，例如烟的味道和气味，以及与吸烟相关的气道感觉，对尼古丁依赖者来说是强大的强化物。这里概述的研究旨在将这些条件强化物与尼古丁的主要强化作用分开，并评估它们对 BOLD fMRI 信号的影响。目的：使用血氧水平依赖性功能磁共振成像来观察吸烟或安慰剂香烟以及尼古丁和盐水输注期间大脑的局部血流动力学变化。药物作用的主观评级也将在整个成像过程中进行测量。涉及尼古丁戒断状态和尼古丁依赖状态的实验将产生数据，揭示这两个因素对吸烟或注射尼古丁或安慰剂对吸烟引起的 BOLD 变化和药物效果主观评价的急性影响的影响。具体目标 1 评估 BOLD 信号变化的时间过程和对吸食烟草的药物效应主观评价：戒断和依赖的影响。具体目标 2：评估 BOLD 信号变化的时间过程和对吸食安慰剂烟草的安慰剂效应主观评级：戒断和依赖的影响。具体目标 3：评估 BOLD 信号变化的时间过程以及对静脉注射药物效果的主观评价。戒断尼古丁依赖吸烟者的尼古丁或盐水输注。理由：之前对尼古丁影响的神经影像学研究使用了吸烟以外的给药途径。由于吸烟是最快速起效的药物作用，并且吸烟是吸烟者使用尼古丁的方法（通常每天数十次），因此更好地了解吸烟尼古丁的影响以及与吸烟相关的条件强化物对吸烟期间大脑激活相关性的影响至关重要。先前的临床和临床前研究支持戒断和依赖可能影响这种效果的观点。吸烟是可预防的主要死亡原因。尽管进行了数十年的研究，但仍然没有有效的治疗烟瘾的方法。更好地了解吸烟尼古丁和安慰剂对活人大脑的影响可能为指导合理有效的治疗方法的开发提供线索。