Department of Psychiatry, Yale University School of Medicine, 2 Church Street South, Suite 109, New Haven, CT 06519, USA.
Nicotine Tob Res. 2012 Nov;14(11):1362-71. doi: 10.1093/ntr/nts090. Epub 2012 Apr 6.
To facilitate translational work in medications development for smoking cessation, we have developed a human laboratory analogue of smoking lapse behavior. Our paradigm models 2 critical features of smoking lapse: the ability to resist the first cigarette and subsequent ad libitum smoking. In this paper we present the results of 2 studies designed to develop and validate the effect of nicotine deprivation on smoking lapse behavior.
Study 1 (n = 30) was designed to develop the model parameters by examining varying levels of nicotine deprivation (1, 6, and 18 hr; within-subject) and identifying optimum levels of monetary reinforcement to provide while modeling the ability to resist smoking. Study 2 was designed to validate the model by screening smoking cessation medications with known clinical efficacy. Subjects (n = 62) were randomized to either varenicline 2 mg/day, bupropion 300 mg/day, or placebo, and we then modeled their ability to resist smoking and subsequent ad libitum smoking.
In Study 1, increasing levels of nicotine deprivation and decreasing levels of monetary reinforcement decreased the ability to resist smoking. In Study 2, the lapse model was found to be sensitive to medication effects among smokers who demonstrated a pattern of heavy, uninterrupted, and automated smoking (i.e., smoked within 5 min of waking). Ratings of craving, mood, withdrawal, and subjective cigarette effects are presented as secondary outcomes with results mirroring clinical findings.
Our smoking lapse model demonstrates promise as a translational tool to screen novel smoking cessation medications. Next steps in this line of research will focus on evaluating predictive validity.
为了促进戒烟药物开发的转化工作，我们开发了一种人类实验室吸烟复发行为模拟。我们的范式模拟了吸烟复发的两个关键特征：抵抗第一支香烟和随后的自由吸烟的能力。在本文中，我们介绍了两项旨在开发和验证尼古丁剥夺对吸烟复发行为影响的研究结果。
研究 1（n=30）旨在通过检查不同程度的尼古丁剥夺（1、6 和 18 小时；个体内）并确定在模拟抵抗吸烟能力时提供最佳货币强化水平来开发模型参数。研究 2 旨在通过筛选具有已知临床疗效的戒烟药物来验证该模型。受试者（n=62）随机分为伐尼克兰 2mg/天、安非他酮 300mg/天或安慰剂组，然后我们对他们的抵抗吸烟和随后的自由吸烟能力进行建模。
在研究 1 中，随着尼古丁剥夺程度的增加和货币强化程度的降低，抵抗吸烟的能力降低。在研究 2 中，发现该复发模型对在表现出大量、不间断和自动化吸烟（即在醒来后 5 分钟内吸烟）的吸烟者中的药物作用敏感。对渴望、情绪、戒断和主观香烟效果的评估作为次要结果呈现，结果与临床发现相吻合。
我们的吸烟复发模型作为一种筛选新型戒烟药物的转化工具具有很大的潜力。该研究领域的下一步将集中评估预测有效性。
