CLOSE ASSOCIATION BETWEEN ALCOHOL AND CIGARETTE USE

饮酒和吸烟之间的密切联系

• 批准号: 6563229
• 负责人: JOHN W ROHRBAUGH
• 金额: $ 17.85万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563229
• 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，酒精和香烟使用之间存在密切联系。一系列实验室挑战研究针对的是这样一种普遍假设，即吸烟可能与过度饮酒有关，因为吸烟降低了人们对酒精醉人效应的敏感度，从而促进了消费增加和成瘾风险。这一普遍假设与两种药物之间交叉耐受性的动物研究的有力证据相一致，也与我们团队对澳大利亚双胞胎样本中的酒精挑战数据进行重新分析的结果一致，该数据显示，急性剂量的酒精在吸烟者中产生的醉酒比不吸烟者少。测量领域将与先前研究中显示的有效范围相同，主要强调使用先进的动态姿势图程序(和互补的动眼运动测试)测量平衡。此外，还将获得药物效果的主观衡量标准。由于他们对尼古丁和酒精的敏感性，将测量他们的心肺反应。这种假设的交叉耐受性将在三项针对21岁至25岁的男性和女性社交饮酒者的研究中进行调查。实验1将对4小时禁烟的吸烟者进行研究，在受控吸烟和急性酒精挑战的同时，与单独服用或既不服用这些物质又不服用这些物质的情况进行比较。在另一次会议中，将评估鼻腔喷雾(NNS)尼古丁的效果，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，尼古丁喷雾将在关键的姿势和眼球运动测量上产生与吸烟相似的效果。实验2将与实验1相似，不同之处在于将向不吸烟的人喷洒尼古丁，以便识别急性影响。实验3将调查适度饮酒的MZ和同性双胞胎DZ对尼古丁依赖的不协调，以提供对未被剥夺的长期吸烟者受到挑战剂量酒精强烈影响的假设的直接和对照测试。对双胞胎的研究将分两个阶段进行，一次是酒精加安慰剂NNS，另一次是酒精加NNS。这项研究的第二个目的是测试交叉耐受性的可能遗传成分，形式是MZ的双胞胎内部差异比DZ双胞胎的小。这些实验的发现将提供关于过度饮酒的潜在重要因素的关键证据。