Reinforcement-enhancing effects of NRT

NRT 的强化作用

• 批准号: 8754436
• 负责人: KENNETH Alan PERKINS
• 金额: $ 26.95万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8754436
• 关键词: Abstinence; Accounting; Acute; Address; Affect; Animal Model; Area; Attenuated; Auditory; Bupropion; Cigarette; Clinical; Cues; Dependence; Drug Kinetics; Environment; Future; Human; Intake; Kinetics; Music; Negative Reinforcements; Neurobiology; Nicotine; Nicotine Dependence; Noise; Nose; Outcome; Pharmaceutical Preparations; Placebos; Predictive Value; Psychological reinforcement; Relapse; Replacement Therapy; Research; Rewards; Rodent; Self-Administered; Sensory; Smoker; Smoking; Specificity; Stimulus; Testing; Therapeutic; Time; Tobacco smoking; Visual; Withdrawal; cigarette smoking; clinical application; clinically relevant; design; drug of abuse; nicotine patch; nicotine replacement; pre-clinical; pre-clinical research; prevent; public health relevance; reinforcer; smoking cessation; success; treatment response; varenicline

DESCRIPTION (provided by applicant): "Reinforcement enhancing effects of NRT" Nicotine clearly has primary and secondary reinforcing effects, as nicotine is self-administered and stimuli associated with nicotine ("cues") can become conditioned reinforcers of responding. Overlooked until recently is non-human research showing that nicotine has a third reinforcing function, that of reinforcement enhancing effects, or increasing reinforcing efficacy of rewards unrelated to nicotine intake. Notably, we recently demonstrated reinforcement enhancing effects, perhaps for the first time in humans, of nicotine intake via tobacco smoking, supporting clinical applicability of these preclinical research findings. Similar effects in both nondependent and dependent smokers and other findings indicated dependence and withdrawal as not necessary for these nicotine effects to occur. Yet, these effects may be specific to only some types of reinforcers, especially positive sensory rewards (visual, auditory, etc.). Also, nicotine' kinetics do not influence its reinforcement enhancing effects in animal models, in contrast to its primary and secondary effects, but reinforcement enhancing effects of rapid versus gradual intake of nicotine per se warrants confirmation in humans. Nicotine via means other than smoking, such as nicotine replacement therapy (NRT), can assess effects of nicotine per se on enhancing reinforcement and determine its clinical predictive value in quitting smokers. NRT also can test if pharmacokinetics influences this reinforcement enhancing effect, via rapid (nasal spray) vs. gradual (patch) nicotine intake. Study 1 will examine influences of nicotine per se (versus placebo) on responding for reinforcers in 60 nondependent and dependent smokers to confirm our results with nicotine via smoking, using our well-validated within-subjects design to increase power. We hypothesize that responding will be greater after NRT (patch or spray) versus placebo, indicating reinforcement enhancing effects of nicotine per se, and we will explore whether these effects differ by type of reward, showing specificity. Study 2 will determine if greater reinforced responding due to NRT early in abstinence predicts days to relapse with NRT in 60 treatment-seeking smokers making a permanent quit attempt. We hypothesize that a greater increase in reinforced responding due to NRT early in cessation will predict longer duration of abstinence. This research is highly significant because demonstrating reinforcement enhancing effects of nicotine per se in humans would have important implications for understanding: an overlooked reinforcing effect of nicotine that may help account for persistence of dependence, some of the efficacy of NRT for aiding smoking cessation, and perhaps potentially similar actions of other therapeutic medications or other drugs of abuse.

描述（由申请人提供）：“尼古丁的增强增强效果显然具有主要和次要增强作用，因为尼古丁是自我管理的，并且与尼古丁（“提示”）相关的刺激可以成为有条件的响应增强剂。直到最近，非人类研究表明尼古丁具有第三个增强功能，增强效应的功能或提高与尼古丁摄入无关的奖励的增强功效。值得注意的是，我们最近证明了通过烟草吸烟的尼古丁摄入的增强效果，也许是第一次在人类中，支持这些临床前研究结果的临床适用性。非依赖性的类似效果 依赖的吸烟者和其他发现表明这些尼古丁作用是不需要的。但是，这些影响可能仅特定于某些类型的增强剂，尤其是积极的感觉奖励（视觉，听觉等）。同样，与其主要和次要作用相比，尼古丁动力学不会影响动物模型中的增强效果，而是增强了尼古丁在人类中的尼古丁本质上的逐渐摄入和逐渐摄入的效果。除吸烟（例如尼古丁替代疗法（NRT））以外的尼古丁通过手段可以评估尼古丁本身对增强增强的影响，并确定其在退出吸烟者中的临床预测价值。 NRT还可以通过快速（鼻喷雾）与逐渐（斑块）尼古丁的摄入来测试药代动力学是否影响这种增强效果。研究1将检查尼古丁本身（与安慰剂）对60名非依赖性和依赖的吸烟者中的增强剂的响应，以通过吸烟确认我们的尼古丁的结果，并使用我们良好的受试者内部设计的设计来增加功率。我们假设在NRT（斑块或喷雾）与安慰剂相比，响应将更大，表明增强尼古丁本身的增强作用，我们将探索这些效果是否因奖励类型而差异，表现出特异性。研究2将确定在禁欲初期由于NRT引起的增强响应是否会预测60名寻求治疗吸烟者的NRT的复发，以永久性地尝试。我们假设，由于戒烟早期，由于NRT引起的增强响应的增加将预测戒酒的持续时间更长。这项研究非常重要，因为证明尼古丁在人类中增强尼古丁的效果对理解具有重要意义：尼古丁的增强作用可能有助于解释依赖性的持续性，NRT对有助于吸烟的某些疗效，以及其他滥用药物或其他虐待药物的其他类似治疗药物的作用。