Reinforcement-enhancing effects of NRT

描述(由申请人提供)：“NRT的强化作用”尼古丁显然具有主要和次要的强化作用，因为尼古丁是自我给予的，与尼古丁相关的刺激(“提示”)可以成为有条件的反应增强剂。直到最近才被忽视的是，非人类的研究表明尼古丁还有第三种增强功能，即增强增强效果，或增加与尼古丁摄入量无关的奖励的增强效果。值得注意的是，我们最近展示了通过吸烟增加尼古丁摄入量的强化效应，这可能是第一次在人类身上，支持了这些临床前研究结果的临床适用性。在两种不依赖的情况下效果相似 而依赖吸烟者和其他发现表明，依赖和戒断并不是这些尼古丁效应发生的必要条件。然而，这些影响可能只对某些类型的增强剂特定，特别是积极的感官奖励(视觉、听觉等)。此外，在动物模型中，尼古丁的动力学不影响其增强作用，与其主要和次要作用相反，但在人类中，尼古丁本身快速摄取与逐渐摄入尼古丁的强化增强作用值得证实。尼古丁通过吸烟以外的方法，如尼古丁替代疗法(NRT)，可以评估尼古丁本身对戒烟者的强化作用，并确定其临床预测价值。NRT还可以通过快速(鼻腔喷雾)和渐进(贴片)尼古丁摄入来测试药代动力学是否影响这种强化效果。研究1将检查尼古丁本身(与安慰剂相比)对60名非依赖和依赖吸烟者对增强剂反应的影响，以证实我们通过吸烟使用尼古丁的结果，使用我们经过充分验证的受试者内设计来增加能量。我们假设，与安慰剂相比，NRT(贴片或喷雾)后的反应将更强，这表明强化增强尼古丁本身的效果，我们将探索这些效果是否因奖励类型而不同，显示出特异性。研究2将确定在戒烟早期由于NRT引起的更大的强化反应是否可以预测60名寻求治疗的吸烟者永久戒烟的NRT复发的天数。我们假设，在戒烟早期，由于NRT引起的强化反应的更大增加将预测更长的戒断持续时间。这项研究意义重大，因为证明尼古丁本身对人类的强化作用对理解尼古丁本身具有重要意义：尼古丁可能有助于解释持久性依赖的被忽视的强化作用，NRT帮助戒烟的一些功效，以及可能与其他治疗药物或其他滥用药物类似的作用。

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.