CLOSE ASSOCIATION BETWEEN ALCOHOL AND CIGARETTE USE

饮酒和吸烟之间的密切联系

• 批准号: 6097766
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-05-11 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6097766
• 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。一系列的实验室挑战性研究的目的是一般假设，吸烟可能是因果关系参与过量饮酒，通过降低急性敏感性的酒精中毒的影响，从而促进消费和成瘾的风险增加。这一一般假设与两种药物之间交叉耐受性的动物研究的有力证据一致，并且与我们对澳大利亚双胞胎样本中酒精挑战数据的重新分析结果一致，该数据显示急性剂量的酒精在吸烟者中产生的中毒比非吸烟者少。测量领域将与先前研究中显示有效的领域相同，主要强调使用先进的动态姿势描记术程序（和补充眼动测试）测量平衡。此外，还将获得药物作用的主观指标。由于他们对尼古丁和酒精的敏感性，将测量他们的呼吸反应。假设的交叉耐受性将在三项研究中进行调查，研究对象为21岁至25岁的男性和女性社交饮酒者。实验1将是一项对4小时剥夺吸烟者的研究，其中受控吸烟将与急性酒精挑战相结合，以与单独给予或不给予物质的条件进行比较。在另一个阶段，将评估尼古丁鼻喷雾剂（NNS）给药的作用，以与吸烟进行比较。假设与先前的动物和神经药理学证据一致，尼古丁喷雾将产生与吸烟对关键姿势图和视力测量结果相似的影响。实验2与实验1相似，不同之处在于将尼古丁喷雾剂给予非吸烟者，以确定急性效应。实验3将调查适度饮酒的MZ和同性DZ双胞胎对尼古丁依赖不一致，提供一个直接和控制的假设，即不受保护的慢性吸烟者强烈影响的酒精的挑战剂量的测试。双胞胎将在两个阶段进行研究，一个是酒精加安慰剂NNS，第二个是酒精加NNS。本研究的第二个目的是测试交叉耐受性的可能遗传成分，即MZ中的对内差异小于DZ双胞胎。这些实验的结果将为过度饮酒的潜在重要因素提供关键证据。