CLOSE ASSOCIATION BETWEEN ALCOHOL AND CIGARETTE USE

饮酒和吸烟之间的密切联系

• 批准号: 6410025
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-01-05 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6410025
• 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，酒精与香烟之间存在密切的关联。一系列实验室挑战研究的一般假设是，通过降低对酒精的醉人敏感性的急性敏感性，吸烟可能与饮酒过度有关，从而促进了增加的消费和成瘾风险。这一普遍的假设与动物研究中两种药物之间交叉耐受性的有力证据是一致的，并且在澳大利亚双胞胎样本中，我们的酒精挑战数据的重新分析的结果表明，急性剂量的酒精剂在吸烟者中的醉酒少于非吸烟者。测量域将与在先前研究中有效的有效域相同，并使用先进的动态姿势术程序（和互补的眼球运动测试）对平衡度量的重视。此外，还将获得药物作用的主观测量。由于对尼古丁和酒精的敏感性，将测量心肺反应。假设的交叉承受能力将在三项男性和女性社会饮酒者的研究中进行研究，21至25岁。实验1将是对4小时剥夺的吸烟者的研究，其中将被控吸烟与急性酒精挑战相结合，以与该物质单独或不给予该物质的条件相比。在额外的会议上，将评估通过鼻喷雾剂（NNS）给药的尼古丁的影响，以与吸烟进行比较。假设是与先前的动物和神经药物证据一致的，即尼古丁喷雾会产生类似于吸烟对关键术后和眼动仪测量的作用。实验2将与实验1相似，只是将尼古丁喷雾剂给予无吸烟者以允许识别急性效应。实验3将研究中度饮用的MZ和同性DZ双胞胎对尼古丁依赖性不一致，以提供直接和控制的测试，即未受繁殖的长期吸烟者受到挑战剂量的酒精剂量的影响。双胞胎将在两次课程中进行研究，一个疗程，一个酒精加安慰剂NN，第二次含酒精加上NNS。这项研究的第二个目的是测试与DZ双胞胎相比，Mz的对成对内差异较小的形式，以跨耐受性测试跨耐受性。这些实验的发现将提供有关过量饮酒的潜在重要贡献者的关键证据。