Behavioral Genetics of Mood-Induced Smoking

描述（由申请人提供）：“情绪诱导吸烟的行为遗传学”对照实验室研究可靠地表明，各种负面情绪操纵会急剧增加吸烟强化。然而，很少有研究确定了个体差异，缓和情绪诱导吸烟，只有一个，我们最近的一份报告，研究了遗传关联。该提案的主要目的是验证我们先前的初步数据，这些数据与由于消极情绪导致的吸烟增加有关，这是尼古丁依赖的一种潜在重要的新表型。依赖性吸烟者（N=200）将参加两个几乎相同的实验室阶段，不同之处仅在于通过经验证的程序诱导消极情绪与积极情绪，以强烈诱导情绪（每个阶段一种情绪，以平衡顺序进行）。在每次情绪诱导过程中，他们会随意抽自己喜欢的牌子的香烟（以最大限度地提高概括性）。消极和积极情绪条件（即情绪诱导的吸烟）之间吸烟强化（潜伏期和吸烟量）的差异将与我们初步研究中鉴定的多巴胺和μ阿片受体基因变体相关。其中包括：多巴胺D4受体（DRD 4 VNTR）、多巴胺D2受体（DRD 2 C957 T SNP [rs6277]和DRD 2/ANKK 1 TaqIA SNP [rs 1800497]）、多巴胺转运蛋白（SLC 6A 3 VNTR）和μ阿片受体外显子1 SNP（OPRM 1 A118 G [rs 1799971]）。在次要目标中，我们将研究与吸烟奖励，影响和相关措施的遗传关联，以及情绪诱导吸烟的其他个体差异，包括受试者性别，抑郁史，痛苦耐受性和尼古丁依赖的严重程度。我们之前的研究以及PI和co-I之间过去富有成效的合作证明了该提案的强大可行性。这个创新项目的结果可能会发现吸烟者由于消极情绪而有更大的复发风险，并可能指导对情绪诱导吸烟机制的研究。我们的程序可以用来测试药物的疗效，以减轻情绪诱导的吸烟，从而减少一些吸烟者的脆弱性，情绪相关的复发。该项目也可以成为未来研究的原型，结合严格的行为药理学方法和遗传学，以确定由于情境影响而导致的药物强化的个体差异。 公共卫生相关性：消极情绪会增加吸烟行为，并导致戒烟尝试后复发。对照实验室研究表明，各种负面情绪操纵（例如压力源）会急剧增加吸烟行为。然而，很少有研究确定了情绪诱发吸烟的个体差异，只有一项研究，即我们的初步研究，研究了情绪诱发吸烟的遗传关联。该项目将验证我们的初步观察，这可能会发现吸烟者特别容易（或抵抗）吸烟复吸由于消极情绪。研究结果可能会指导环境对吸烟行为和其他药物滥用影响的遗传学研究，并可能指导情绪诱导吸烟背后机制的研究。

DESCRIPTION (provided by applicant): "Behavioral Genetics of Mood-Induced Smoking" Controlled laboratory studies reliably show that negative mood manipulations of various kinds acutely increase smoking reinforcement. However, very few studies have identified individual differences that moderate mood-induced smoking, and only one, a recent report by us, has examined genetic associations. The primary aim of this proposal is to validate our prior, preliminary data on genetic associations with increases in smoking due to negative mood, a potentially important novel phenotype for nicotine dependence. Dependent smokers (N=200) will participate in two virtually identical lab sessions, differing only in induction of negative vs. positive mood via a validated procedure to robustly induce mood (one mood per session, sessions in counter-balanced order). They will ad lib smoke their preferred brand of cigarettes (to maximize generalizability) during mood induction each session. Differences in smoking reinforcement (latency and amount of smoking) between the negative and positive mood conditions, i.e. mood-induced smoking, will be related to the dopamine and mu opioid receptor gene variants identified in our preliminary study. These include: dopamine D4 receptor (DRD4 VNTR), dopamine D2 receptor (DRD2 C957T SNP [rs6277] and DRD2/ANKK1 TaqIA SNP [rs1800497]), the dopamine transporter (SLC6A3 VNTR), and the mu opioid receptor exon 1 SNP (OPRM1 A118G [rs1799971]). In secondary aims, we will examine genetic associations with smoking reward, affect, and related measures, as well as other individual differences in mood-induced smoking, including subject sex, depression history, distress tolerance, and severity of nicotine dependence. Our prior study and past productive collaborations between the PI and co-I demonstrate the strong feasibility of this proposal. Results of this innovative project may identify smokers potentially at greater risk for relapse due to negative mood and may guide research on mechanisms behind mood-induced smoking. Our procedures could be used to test the efficacy of medications to attenuate mood-induced smoking, thereby reducing vulnerability of some smokers to mood-related relapse. This project also could be a prototype for future research that combines rigorous behavioral pharmacology methodology and genetics to identify individual variation in drug reinforcement due to situational influences. PUBLIC HEALTH RELEVANCE: Negative mood increases smoking behavior and leads to relapse after a quit attempt. Controlled laboratory studies show that negative mood manipulations of various kinds (e.g. stressors) acutely increase smoking behavior. However, very few studies have identified individual differences in mood-induced smoking, and only one, a preliminary study by us, examined genetic associations with mood-induced smoking. This project will validate our preliminary observations, which may identify smokers particularly vulnerable (or resistant) to smoking relapse due to negative mood. Results may guide research on genetics of environmental influences on smoking behavior and other drug abuse, and perhaps guide research on the mechanisms behind mood-induced smoking.