Mechanisms of Smoking Reinforcement

描述（由申请人提供）：广泛的研究表明，尼古丁在实验动物和人类中都是一种初级强化物，与尼古丁传递相关的感觉运动刺激可以作为条件强化物。然而，一些观察结果表明，这两种机制（即原始强化和条件强化）不能充分解释吸烟强化。尼古丁是一种相对弱的强化物，当它单独出现时（即没有任何其他刺激），可能不会产生离散的强化神经生物学事件，而这些事件是大多数初级强化模型的重要组成部分，并且与尼古丁相关的刺激协同作用以强化操作行为。最近的临床前研究发现了尼古丁的一种新作用，这可能有助于解释这些观察结果，并有助于更好地理解尼古丁在吸烟强化中的作用。尼古丁极大地促进了其他刺激物的强化特性，而这种增强特性并不依赖于刺激物与尼古丁的时间或因果关系。这些发现表明，尼古丁可能以两种不同的方式驱动吸烟行为——首先，作为初级强化物，从而在尼古丁相关刺激上传递条件强化特性；其次，通过直接增强吸烟的其他强化特性（例如，来自吸烟刺激的条件强化）。这里提出的实验通过检测多剂量透皮尼古丁对主观、生理和强化效应的影响来验证这一假设，这些影响是在受控的实验室环境和自然环境中暴露多日的无尼古丁香烟。鉴于烟草使用对健康造成的严重后果，进一步了解尼古丁在吸烟强化中的作用至关重要。

DESCRIPTION (provided by applicant): Extensive research has shown that nicotine functions as a primary reinforcer in both laboratory animals and humans and that the sensorimotor stimuli associated with nicotine delivery can act as conditioned reinforcers. However, several observations suggest that these two mechanisms (i.e., primary and conditioned reinforcement) cannot adequately explain smoking reinforcement. Nicotine is a relatively weak reinforcer when it is presented by itself (i.e., without any other stimuli), may not produce the discrete reinforcing neurobiological events that are an essential component of most primary reinforcement models, and interacts synergistically with nicotine-associated stimuli to reinforcer operant behavior. Recent preclinical research has uncovered a novel effect of nicotine that may help explain these observations and lead to a better understanding of the role of nicotine in smoking reinforcement. Nicotine greatly facilitates the reinforcing properties of other stimuli in a manner that is not dependent on the stimuli being temporally or causally related to nicotine. These findings suggest that nicotine may drive smoking behavior in two distinct ways - first, by acting as a primary reinforcer and consequently conveying conditioned reinforcing properties on nicotine-associated stimuli, and second, by directly potentiating other reinforcing properties of smoking (e.g., the conditioned reinforcement derived from smoking stimuli). The experiment proposed here tests this hypothesis by examining the effects of multiple doses of transdermal nicotine on the subjective, physiological, and reinforcing effects of nicotine-free cigarettes over multiple days of exposure in both a controlled laboratory setting and the natural environment. Given the grave health consequences of tobacco use, further understanding of the role of nicotine in smoking reinforcement is critically important.