Reinforcement-enhancing effects of nicotine

尼古丁的强化作用

• 批准号: 8087136
• 负责人: KENNETH Alan PERKINS
• 金额: $ 18.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8087136
• 关键词: Abstinence; Acute; Anhedonia; Animal Experimentation; Animal Model; Animals; Chronic; Cigarette; Computers; Dependence; Development; Environment; Failure; Familiarity; Future; Human; Intake; Lead; Link; Mental Depression; Music; Nicotine; Nicotine Dependence; Noise; Pharmaceutical Preparations; Procedures; Psychological reinforcement; Relapse; Research; Research Project Grants; Rewards; Rodent; Self-Administered; Sex Characteristics; Smoker; Smoking; Smoking Behavior; Stimulus; Sum; United States National Institutes of Health; Withdrawal; Withholding Treatment; Woman; Work; cigarette smoking; design; improved; men; prevent; programs; reinforcer; smoking cessation; success

DESCRIPTION (provided by applicant): "Reinforcement-enhancing effects of nicotine" Nicotine clearly has primary and secondary reinforcing effects in humans and animal models. Very recent research in rodents indicates that nicotine may also have a third reinforcing function; that of reinforcement-enhancing effects, or increasing the reinforcing efficacy of rewards unrelated to nicotine intake. This R21 application seeks to determine whether nicotine via smoking has reinforcement enhancing effects in humans. One hundred smokers, 50 nicotine dependent and 50 nondependent, will participate in 4 experimental sessions, involving: 1) smoking nicotine (0.6 mg) cigarettes or 2) smoking denic (0.05 mg) cigarettes or 3) no smoking, each after overnight abstinence, or 4) smoking their own brand after no overnight abstinence (exploratory condition). In each session, they will respond on a simple operant task for small amounts of money, brief access to preferred music, avoidance of aversive white noise, or no reward (control). Our primary specific aim is to examine the influence of nicotine via smoking on responding for rewards. We hypothesize that reinforced responding will be greater after smoking a nicotine vs a denic cigarette (and vs. no smoking), indicating reinforcement enhancing effects of nicotine per se. Effects of nicotine on responding for some rewards versus others or no reward will indicate that reinforcement enhancement due to nicotine is specific to certain rewards and not a generalized effect of nicotine intake. Reinforcement-enhancing effects of nicotine in nondependent smokers, as well as dependent smokers, would suggest that these effects do not require the establishment of dependence and reflect absolute enhancement of reinforcement, as observed in the rodent studies. Substantial pilot work supports project feasibility and points to the likelihood of these hypothesized results. By contrast, if effects are observed only in dependent and not nondependent smokers, they could reflect withdrawal relief and not true enhancement of reinforcement. A secondary aim is to explore sex differences in the reinforcement enhancing effects of nicotine. This research is highly significant because demonstrating reinforcement-enhancing effects of nicotine in humans would have very important implications for our understanding of nicotine dependence. It would indicate that smoking does not "just" provide reinforcement from direct psychoactive effects of nicotine but rather broadly increases the reinforcing effects of the other rewards in a smoker's environment. Therefore, quitting smoking would result in a loss of this broad reinforcement, in addition to loss of nicotine's psychoactive effects. This broad reinforcement loss could be restored by smoking one cigarette (i.e. a lapse), helping to explain the persistence of smoking behavior. Results would provide directions for improving cessation treatments. This R21 submission fits the requirements of PA-10-069, "NIH Exploratory Developmental Research Grant Program." PUBLIC HEALTH RELEVANCE: "Reinforcement enhancing effects of nicotine" This project will determine whether nicotine via cigarette smoking increases the reinforcing value of other rewards unrelated to smoking, as indicated by recent rodent studies. Dependent and nondependent smokers will work on a computer task to earn various small rewards after smoking nicotine or denic cigarettes or not smoking. This research is highly significant because demonstrating reinforcement-enhancing effects of nicotine in humans would have very important implications for our understanding of nicotine dependence. It would indicate that smoking does not "just" provide reinforcement from direct psychoactive effects of nicotine, but rather broadly increases the reinforcing effects of the other rewards in a smoker's environment. Therefore, quitting smoking could result in a loss of this broad reinforcement, in addition to loss of nicotine's psychoactive effects. This broad reinforcement loss could be restored by smoking a cigarette (i.e. a lapse), helping to explain why a lapse almost invariably leads to relapse after a quit attempt.

描述（由申请人提供）：“尼古丁的增强作用”尼古丁在人类和动物模型中明显具有主要和次要的增强作用。最近对啮齿动物的研究表明，尼古丁还可能具有第三种强化功能;即增强食欲的作用，或增加与尼古丁摄入无关的奖励的强化功效。这项R21申请旨在确定通过吸烟的尼古丁是否对人类具有强化增强作用。100名吸烟者（50名尼古丁依赖者和50名非依赖者）将参加4个实验阶段，包括：1）吸烟尼古丁（0.6 mg）香烟或2）吸烟denic（0.05 mg）香烟或3）戒烟，均在整夜戒烟后，或4）在整夜戒烟后吸烟自己的品牌（探索性条件）。在每一阶段，他们将对一个简单的操作性任务做出反应，条件是少量的钱，短暂地接触喜欢的音乐，避免令人厌恶的白色噪音，或者没有奖励（控制）。我们的主要具体目标是研究尼古丁通过吸烟对奖励反应的影响。我们假设，吸烟尼古丁后的强化反应将大于非吸烟香烟（和不吸烟），表明尼古丁本身的强化增强效应。尼古丁对某些奖励与其他奖励或无奖励的反应的影响表明，尼古丁引起的强化增强是特定于某些奖励的，而不是尼古丁摄入的普遍效应。尼古丁在非依赖性吸烟者和依赖性吸烟者中的强化增强作用表明，这些作用不需要建立依赖性，而是反映了强化的绝对增强，如啮齿动物研究中所观察到的那样。大量的试点工作支持项目的可行性，并指出这些假设结果的可能性。相比之下，如果仅在依赖性吸烟者而非依赖性吸烟者中观察到效果，则它们可能反映了戒断缓解，而不是真正的强化增强。第二个目的是探索尼古丁强化增强效应的性别差异。这项研究非常重要，因为证明尼古丁在人类中的增强作用将对我们理解尼古丁依赖具有非常重要的意义。这表明，吸烟并不“只是”提供尼古丁直接精神作用的强化，而是广泛地增加了吸烟者环境中其他奖励的强化作用。因此，戒烟将导致这种广泛的强化作用的丧失，以及尼古丁的精神活性作用的丧失。这种广泛的强化损失可以通过吸一支烟（即一次失误）来恢复，这有助于解释吸烟行为的持续性。研究结果将为改善戒烟治疗提供指导。本R21申报符合PA-10-069“NIH探索性发展研究资助计划”的要求。" 公共卫生关系：“尼古丁的强化增强作用”本项目将确定通过吸烟产生的尼古丁是否会增加与吸烟无关的其他奖励的强化价值，正如最近的啮齿动物研究所表明的那样。依赖性和非依赖性吸烟者将工作在一个计算机任务，以赚取各种小奖励后，吸烟尼古丁或丹麦香烟或不吸烟。这项研究非常重要，因为证明尼古丁在人类中的增强作用将对我们理解尼古丁依赖具有非常重要的意义。这表明，吸烟并不“仅仅”提供尼古丁直接精神作用的强化，而是广泛地增加了吸烟者环境中其他奖励的强化作用。因此，戒烟可能会导致这种广泛的强化作用的丧失，以及尼古丁的精神活性作用的丧失。这种广泛的强化损失可以通过吸烟（即失误）来恢复，这有助于解释为什么失误几乎总是导致戒烟尝试后的复发。