Reinforcement-enhancing effects of nicotine

尼古丁的强化作用

基本信息

批准号：
8302290
负责人：
KENNETH Alan PERKINS
金额：
$ 22.73万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-15 至 2015-04-30
项目状态：
已结题

项目摘要

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."

描述（由申请人提供）：“尼古丁的增强增强效应”尼古丁显然在人类和动物模型中具有主要和次要的增强作用。最近对啮齿动物的研究表明，尼古丁也可能具有第三个增强功能。增强增强作用，或提高与尼古丁摄入无关的奖励的增强功效。该R21应用程序旨在确定通过吸烟的尼古丁是否具有增强对人类的增强作用。 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).在每个会话中，他们都会以少量金钱的简单操作任务做出响应，简短地访问首选音乐，避免厌恶的白噪声或没有奖励（控制）。我们的主要目的是通过吸烟来检查尼古丁对奖励的反应。我们假设在吸烟尼古丁与否认香烟（和无吸烟）后，得到的增强反应会更大，这表明增强了尼古丁本身的增强作用。尼古丁对一些奖励与其他奖励的反应或没有奖励的影响将表明，尼古丁引起的增强是特定于某些奖励的，而不是尼古丁摄入的一般效果。尼古丁在非依赖性吸烟者以及依赖的吸烟者中的增强增强作用会表明，这些作用不需要建立依赖性，并反映了啮齿动物研究中观察到的强化的绝对增强。实质性的飞行员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，如果仅在依赖和非依赖性吸烟者中观察到效果，它们可以反映戒断的缓解，而不是真正增强增强的效果。第二个目的是探索增强尼古丁效果的性别差异。这项研究非常重要，因为证明尼古丁在人类中的增强增强作用将对我们对尼古丁依赖性的理解具有非常重要的意义。这表明吸烟不会“仅”从尼古丁的直接精神活性作用提供增强，而是广泛地增加了其他奖励在吸烟者环境中的增强作用。因此，除了失去尼古丁的精神活性作用外，戒烟还会导致这种广泛的增强。通过吸烟（即失误），可以恢复这种广泛的加强损失，有助于解释吸烟行为的持久性。结果将为改善戒烟治疗提供指导。该R21提交符合PA-10-069的要求，即“ NIH探索性发展研究赠款计划”。