Does smoking cessation cause anhedonia? A test of pre-clinical findings

戒烟会导致快感缺乏吗？

• 批准号: 8145477
• 负责人: JOHN R HUGHES
• 金额: $ 30.66万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145477
• 关键词: Abstinence; Acute; Affective; Anhedonia; Animal Experimentation; Animal Model; Animals; Back; Behavior Therapy; Behavioral; Chronic; Clinical; Clinical Data; Communities; Event; Exhibits; Exposure to; Human; Incidence; Intervention; Measures; Mental Depression; Methods; Modeling; Modification; Motivation; Nicotine; Nicotine Withdrawal; Patient Self-Report; Pattern; Pharmacological Treatment; Pre-Clinical Model; Process; Psychological reinforcement; Psychotherapy; Recruitment Activity; Relapse; Reporting; Research Personnel; Rewards; Schedule; Selection Bias; Smoke; Smoker; Smoking; Symptoms; Testing; Time; Tobacco; Tobacco Dependence; Withdrawal; Withdrawal Symptom; base; comparison group; pleasure; pre-clinical; smoking cessation; tobacco abstinence

DESCRIPTION (provided by applicant): Recent animal research indicates acute nicotine increases the reinforcing effects of other rewards; however, chronic use of nicotine recruits an opponent process that counteracts the acute effects of nicotine and decreases sensitivity to rewards. When nicotine is discontinued in animals, this opponent process persists and the resultant decreased sensitivity to rewards may be a cause of nicotine withdrawal symptoms such as depression and a cause of relapse back to smoking. Although this animal model is widely cited, whether decreased reward sensitivity occurs when smokers stop smoking is unclear. The investigators propose an experimental test that focuses on whether abstinent smokers a) are less sensitive to monetary rewards during an operant task and/or b) report anhedonia (less pleasure from rewards) and apathy (less motivation to seek rewards). The investigators will recruit 120 current smokers who plan to quit smoking for good to smoke their usual amount for one week and then will abstain for 4 weeks. To insure an adequate number of continuously abstinent smokers and to decrease selection bias, they will use monetary contingencies to encourage abstinence. The investigators anticipate this will produce > 70 smokers who remain abstinent for all 4 weeks. To assist in interpretation of results, they will also recruit a comparison group of 70 long-abstinent former smokers to be measured on the same schedule. The investigators will measure reward sensitivity three times each week using a) progressive ratio (PR) responding for monetary rewards and b) self-report measures of anhedonia and apathy scales. If reward sensitivity changes with abstinence, secondary aims will be to determine a) its magnitude, incidence and time course; b) whether it exhibits the time course expected of a withdrawal effect, c) whether reward sensitivity becomes similar to the level among long-abstinent smokers and c) whether decreased reward sensitivity could be the basis for much of withdrawal discomfort. The results of this study will be an important translational test of the leading animal model of nicotine withdrawal. If decreased reward sensitivity is found, this would suggest revisions in clinical descriptions of nicotine withdrawal, new targets for behavioral and pharmacological interventions and new treatments for smoking cessation (e.g., increased exposure to rewarding events). If reward sensitivity does not change with abstinence, then (given the adequacy of the investigators' test) this would suggest a widely cited animal model of abstinence effects may not be generalizable to human attempts to stop smoking. PUBLIC HEALTH RELEVANCE: The most widely-accepted animal model of nicotine withdrawal states stopping nicotine makes rewarding events become less rewarding. The current study will test if this is true in humans. If the investigators find tobacco abstinence does make rewards less rewarding, this would suggest new symptoms to add to official descriptions of nicotine withdrawal. It would also suggest the need to develop new behavioral and pharmacological interventions to correct this problem. If stopping smoking does not make rewards less rewarding, this would suggest that this animal model does not apply to the human condition and a need to continue the search for an animal model of tobacco withdrawal that is relevant to smokers' stopping smoking.

描述（由申请人提供）：最近的动物研究表明，急性尼古丁会增加其他奖励的强化作用;然而，长期使用尼古丁会招募一个对抗过程，抵消尼古丁的急性作用并降低对奖励的敏感性。当尼古丁在动物中停止使用时，这种对抗过程持续存在，并且由此产生的对奖励的敏感性降低可能是尼古丁戒断症状（如抑郁症）的原因，也是重新吸烟的原因。虽然这种动物模型被广泛引用，但当吸烟者停止吸烟时，奖励敏感性是否会降低还不清楚。研究人员提出了一个实验测试，重点是戒烟者是否a）在操作性任务中对金钱奖励不太敏感和/或B）报告快感缺乏（奖励带来的快乐减少）和冷漠（寻求奖励的动机减少）。研究人员将招募120名计划戒烟的吸烟者，他们将在一周内吸烟，然后戒烟4周。为了确保有足够数量的持续戒烟的吸烟者和减少选择偏差，他们将使用货币应急措施来鼓励戒烟。研究人员预计，这将产生超过70名吸烟者，他们在所有4周内保持戒烟。为了帮助解释结果，他们还将招募70名长期戒烟的前吸烟者作为对照组，按照相同的时间表进行测量。研究者将每周测量三次奖励敏感性，使用a）对金钱奖励的反应的累进比率（PR）和B）快感缺乏和冷漠量表的自我报告测量。如果奖赏敏感性随着戒烟而改变，那么次要目标将是确定a）其幅度、发生率和时间进程; B）它是否表现出预期的戒断效应的时间进程; c）奖赏敏感性是否变得与长期戒烟者的水平相似;以及c）奖赏敏感性降低是否可能是大部分戒断不适的基础。本研究的结果将是尼古丁戒断的主要动物模型的重要转化试验。如果发现奖赏敏感性降低，这将建议修改尼古丁戒断的临床描述，行为和药理干预的新目标以及戒烟的新治疗方法（例如，增加对奖励活动的接触）。如果奖励敏感性不随戒烟而改变，那么（考虑到研究人员的测试的充分性）这将表明一个被广泛引用的戒烟效应的动物模型可能无法推广到人类戒烟的尝试。 公共卫生关系：最被广泛接受的尼古丁戒断动物模型表明，停止尼古丁会使奖励事件变得不那么有益。目前的研究将测试这在人类中是否属实。如果研究人员发现戒烟确实使奖励减少，这将表明新的症状添加到尼古丁戒断的官方描述中。这也表明需要开发新的行为和药理干预措施来纠正这个问题。如果停止吸烟不会使奖励减少，这将表明这种动物模型不适用于人类状况，需要继续寻找与吸烟者戒烟相关的烟草戒断动物模型。