Nicotine dependence, withdrawal and replacement therapy assessed by PET imaging

描述（由申请人提供）：虽然在过去二十年中，男性和女性的吸烟率都有所下降，但女性的吸烟率下降幅度要小得多，近年来，女孩开始吸烟的流行率高于男孩。育龄妇女吸烟对母亲和儿童的健康产生严重的负面影响，增加了胎儿和婴儿的发病率和死亡率。女性不太可能主动尝试戒烟，如果真的戒烟，她们更有可能复发。尼古丁替代疗法（NRT）仍然是美国最广泛使用的吸烟治疗干预措施，与男性相比，对女性的有效性较低，女性对NRT的渴望减少较少。内源性阿片系统参与吸烟启动、尼古丁渴求和奖赏以及尼古丁戒断症状。有趣的是，研究表明，内源性μ-阿片系统的性二态特征可能部分解释了尼古丁效应的性别差异。为了更好地了解μ阿片系统在女性NRT反应较差中的作用，本提案将在活性与安慰剂NRT期间，与男性吸烟者相比，检查NRT对女性μ阿片受体结合潜力（莫尔BP）的影响。具体而言，处于主动吸烟状态的尼古丁依赖女性和男性将接受PET成像，使用11 C-卡芬太尼测量莫尔血压。在主动吸烟的基线PET测量（扫描1）后，吸烟者将随机接受活性或安慰剂尼古丁替代治疗（（A-NRT或P-NRT））; 72小时后，将进行第二次扫描。作为参考组，人口统计学上匹配的从未吸烟的女性和男性也将接受两次扫描。将在整个方案中重复获得尼古丁奖赏、渴望和戒断的行为测量值。拟议的研究将提供关于μ阿片系统在尼古丁依赖和尼古丁替代疗法的治疗有效性中的功能的科学和临床相关的重要的新的、性别特异性信息。

DESCRIPTION (provided by applicant): While smoking prevalence has declined for both men and women over the last two decades, rates among women have shown a much shallower decrease and, in recent years, prevalence of cigarette initiation has been higher for girls than boys. Smoking among women of child-bearing age has significant negative health consequences for mother and child, increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a quit attempt and more likely to relapse if they do quit. Nicotine replacement therapy (NRT), still the most widely used smoking treatment intervention in the United States, is less effective for women compared with men, and women report less craving reduction on NRT. The endogenous opioid system is involved in smoking initiation, nicotine craving and reward as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic features of the endogenous mu-opioid system may in part explain gender differences in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT responses in women, this proposal will examine NRT effects on mu opioid receptor binding potential (MOR BP) in female compared to male smokers during active versus placebo NRT. Specifically, nicotine dependent women and men in active smoking status will undergo PET imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference group, demographically-matched women and men who have never smoked will undergo two scans as well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained repeatedly across the protocol. The proposed research will provide significant new, gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy.