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，女孩的吸烟率高于男孩。育龄妇女吸烟对母亲和儿童的健康有严重的负面影响，增加了胎儿和婴儿的发病率和死亡率。女性开始尝试戒烟的可能性更小，如果她们戒烟了，复发的可能性更大。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，女性的效果较差，女性报告的尼古丁替代疗法减少的渴望程度较低。内源性阿片系统参与吸烟开始，尼古丁渴望和奖励以及尼古丁戒断症状。有趣的是，研究表明，内源性mu-阿片系统的两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mu-阿片系统在女性较差的NRT反应中的作用，本提案将研究NRT对女性吸烟者和男性吸烟者在主动和安慰剂NRT期间的mu阿片受体结合电位（MOR BP）的影响。具体地说，尼古丁依赖的女性和处于活跃吸烟状态的男性将使用11c -卡芬太尼进行PET成像进行MOR BP测量。在主动吸烟的基线PET测量（扫描1）之后，吸烟者将随机接受主动或安慰剂尼古丁替代治疗((A-NRT或P-NRT)；72小时后，将获得第二次扫描。作为参照组，人口统计学匹配的从不吸烟的女性和男性也将接受两次扫描。行为测量尼古丁奖励，渴望和戒断将在整个方案中反复获得。本研究将提供重要的、新的、性别特异性的、具有科学和临床意义的信息，以了解多阿片系统在尼古丁依赖中的功能和尼古丁替代疗法的治疗效果。

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.