CLOSE ASSOCIATION BETWEEN ALCOHOL AND CIGARETTE USE

饮酒和吸烟之间的密切联系

• 批准号: 6299198
• 负责人: JOHN W ROHRBAUGH
• 金额: $ 13.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299198
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; balance; clinical research; dizygotic twins; drug interactions; drug tolerance; eye movements; family genetics; genetic susceptibility; heart function; human subject; inhalation drug administration; monozygotic twins; nicotine; pharmacogenetics; posture; pulmonary respiration; tobacco abuse; young adult human (21-34)

Substantial evidence points to a close association between alcohol and cigarette use. A sequence of laboratory challenge studies is aimed at the general hypothesis that cigarette smoking may be causally involved in excessive drinking by decreasing the acute sensitivity to the intoxicating effects of alcohol, thereby promoted increased consumption and risk of addiction. This general hypothesis is consistent with strong evidence from animal studies of cross-tolerance between the two drugs, and with findings from a reanalysis by our group of alcohol challenge data in a Australian twin sample showing that an acute dose of alcohol produced less intoxication in smokers than in non-smokers. Measurement domains will be the same as those shown effective in prior studies, with principal emphasis on measures of balance using advanced dynamic posturography procedures (and complementary oculomotor tests). In addition subjective measures of drug effects will be obtained. Cardiorespiratory responses will be measured because of their sensitivity to nicotine as well as alcohol. The hypothesized cross- tolerance will be investigated in three studies of male and female social drinkers, ages 21 through 25. Experiment 1 will be a study of 4- hour deprived smokers in which controlled cigarette smoking will be combined with acute alcohol challenges, for comparison with conditions in which the substances are given individually or neither is administered. In an additional session, the effects of nicotine administered by nasal spray (NNS) will be assessed for comparison with smoking. It is hypothesized, consistent with prior animal and neuropharmacological evidence, that nicotine spray will produce effects similar to those seen with smoking on the critical posturographic and oculomotor measures. Experiment 2 will be similar to Experiment 1, except that nicotine spray will be given to no-smokers to allow acute effects to be identified. Experiment 3 will investigate moderate drinking MZ and same-sex DZ twin pairs discordant for nicotine dependence, to provide a direct and controlled test of the hypothesis that undeprived chronic smokers are intensely affected by a challenge dose of alcohol. Twins will be studied in two sessions, one with alcohol plus placebo NNS, and a second with alcohol plus NNS. A second aim from this study is to test for a possible genetic component to the cross tolerance, in the form of smaller intra-pair differences in MZ than in DZ twins. The findings from these experiments will provide critical evidence regarding a potential important contributor to excessive drinking.

大量证据表明，饮酒和吸烟之间存在密切联系。一系列实验室挑战研究的目标是一般假设，即吸烟可能与过度饮酒有因果关系，因为吸烟降低了对酒精中毒作用的急性敏感性，从而增加了消费和成瘾的风险。这一普遍假设与两种药物交叉耐受性的动物研究的有力证据相一致，也与我们小组对澳大利亚双胞胎样本的酒精挑战数据的再分析结果相一致，结果显示急性剂量的酒精在吸烟者中产生的中毒比在非吸烟者中产生的中毒少。测量领域将与先前研究中显示的有效领域相同，主要强调使用先进的动态姿势测量程序（和互补的动眼肌测试）来测量平衡。此外，还将获得药物效应的主观度量。将测量心肺反应，因为它们对尼古丁和酒精都很敏感。假设的交叉耐受将在三项研究中进行调查，研究对象为21至25岁的男性和女性社交饮酒者。实验1将是一项对被剥夺4小时吸烟时间的吸烟者的研究，在这项研究中，受控的吸烟将与急性酒精挑战相结合，以与单独给予这些物质或两者都不给予的情况进行比较。在另一个环节，将评估鼻腔喷雾剂（NNS）对尼古丁的影响，并与吸烟进行比较。与先前的动物和神经药理学证据相一致的假设是，尼古丁喷雾剂在关键的姿势和动眼力测量方面产生的效果与吸烟相似。实验2将与实验1类似，除了尼古丁喷雾将给不吸烟者，以便确定急性效果。实验3将研究中度饮酒的MZ和同性DZ对尼古丁依赖不一致的双胞胎，为未剥夺的慢性吸烟者受到挑战剂量酒精的强烈影响这一假设提供直接和对照的检验。双胞胎将分两个阶段进行研究，一个是酒精加安慰剂神经刺激疗法，另一个是酒精加神经刺激疗法。这项研究的第二个目的是测试交叉耐受性可能的遗传成分，以MZ比DZ双胞胎更小的对内差异的形式。这些实验的发现将为过量饮酒的潜在重要因素提供关键证据。