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，各种负面情绪控制显著增加吸烟强化。然而，很少有研究确定适度情绪导致吸烟的个体差异，只有一项研究，我们最近的一份报告，研究了遗传联系。这项建议的主要目的是验证我们先前关于负性情绪导致吸烟增加的遗传相关性的初步数据，负性情绪是尼古丁依赖的一种潜在的重要新表型。依赖型吸烟者(N=200)将参加两个几乎相同的实验室实验，不同之处只在于通过有效的程序诱导积极情绪和消极情绪(每次一个情绪，按相反的顺序进行)。他们将在每一次情绪诱导期间随意抽他们喜欢的香烟品牌(以最大限度地提高普适性)。消极情绪状态和积极情绪状态下吸烟强化(潜伏期和吸烟量)的差异，即情绪诱导吸烟，将与我们初步研究中发现的多巴胺和u阿片受体基因变异有关。这些基因包括：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u阿片受体外显子1 SNP(OPRM1 A118G[rs1799971])。在次要目标中，我们将检查吸烟奖赏、情感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。我们先前的研究和过去PI和co-I之间富有成效的合作证明了这一建议的强大可行性。这一创新项目的结果可能会确定吸烟者由于负面情绪而可能面临更大的复发风险，并可能指导对情绪诱导吸烟背后机制的研究。我们的程序可以用来测试减轻情绪引起的吸烟的药物的有效性，从而降低一些吸烟者对情绪相关复发的易感性。该项目也可能成为未来研究的原型，该研究将严格的行为药理学方法论和遗传学相结合，以确定由于情景影响而在药物强化方面的个体差异。 公共卫生相关性：负面情绪会增加吸烟行为，并导致戒烟尝试后复发。受控的实验室研究表明，各种负面情绪控制(例如，应激源)会显著增加吸烟行为。然而，很少有研究确定情绪性吸烟的个体差异，只有一项初步研究检验了与情绪性吸烟的遗传联系。这个项目将验证我们的初步观察，这些观察可能会发现吸烟者特别容易(或抵制)由于负面情绪而重新吸烟。这些结果可能会指导环境对吸烟行为和其他药物滥用的遗传学影响的研究，也可能指导对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.