Behavioral Genetics of Mood-Induced Smoking

描述（由申请人提供）：“情绪诱发吸烟的行为遗传学”受控实验室研究可靠地表明，各种消极情绪操纵急剧增加吸烟强化。然而，很少有研究确定了适度情绪诱导吸烟的个体差异，只有一项研究（我们最近的一份报告）研究了遗传关联。这项提议的主要目的是验证我们之前的初步数据，即消极情绪与吸烟增加的遗传关联，消极情绪是尼古丁依赖的一种潜在重要的新表型。依赖吸烟者（N=200）将参加两个几乎相同的实验阶段，通过一个有效的程序来诱导情绪（每次一种情绪，以平衡顺序进行），仅在诱导消极情绪和积极情绪方面有所不同。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（以最大限度地提高普遍性）。在消极和积极情绪条件下，即情绪诱导吸烟，吸烟强化（潜伏期和吸烟量）的差异将与我们初步研究中发现的多巴胺和mu阿片受体基因变异有关。这些包括：多巴胺D4受体（DRD4 VNTR）、多巴胺D2受体（DRD2 C957T SNP [rs6277]和DRD2/ANKK1 TaqIA SNP [rs1800497]）、多巴胺转运蛋白（SLC6A3 VNTR）和mu阿片受体外显子1 SNP （OPRM1 A118G [rs1799971]）。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。我们之前的研究和PI与co-I之间过去富有成效的合作证明了这一建议的可行性。这一创新项目的结果可能会确定吸烟者由于消极情绪而复发的潜在风险更大，并可能指导情绪诱发吸烟背后机制的研究。我们的程序可以用来测试药物的有效性，以减轻情绪引起的吸烟，从而减少一些吸烟者对情绪相关复发的脆弱性。这个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来识别由于环境影响而导致的药物强化的个体差异。

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.