HUMAN BRAIN NICOTINIC RECEPTORS AND NICOTINE ADDICTION

卫生局局长承认每个人的贪婪程度不同 对烟草的支持和回应*美国农业部)，1988)暗示可能存在 决定人类吸烟习惯的遗传差异。的可变性 由于人类群体中的遗传差异，基因表达可能 确定观察到的行为或生理反应的差异 环境影响因素，包括吸烟。单合子和单卵的研究 同卵双胞胎表明，两个双胞胎的吸烟发生率都是 在同卵双胞胎中更高，以及 吸烟习惯。尼古丁敏感性的动物模型(小鼠)表明 约35%-40%的人对尼古丁的初始反应 不同的小鼠品系是由于数量和数量的不同 尼古丁受体在大脑中的分布。容忍或上瘾 因此，尼古丁在人类体内的作用可能与个体差异有关。 烟碱型乙酰胆碱受体家族。这个基因家族是复杂的 已知亚基以不同的不同组合形式存在 尼古丁的亲和力，可能与人体功能有关的差异 确定一个人是否对烟草上瘾。这个 拟议的研究将检验这样一个假设，即尼古丁 人死后脑中存在受体的表达或功能， 这些差异可能与吸烟史有关。我们将衡量 死后脑内烟碱受体家族的区域结合 在吸烟者和非吸烟者之间，表征了mRNA的区域表达 三个烟碱受体亚基，并确定区域功能 这些受体的状态。将这项研究的结果与 受试者的生活吸烟史，将提供关于 该受体家族在尼古丁成瘾中的重要性。

Recognition by the Surgeon General that individuals differ in their avidity for and responses to tobacco *USDA), 1988) implies that there could be heritable differences determining human smoking habits. Variability in gene expression, due to genetic differences in the human population, may determine differences in observed behaviors or physiological responses to environmental effectors, including smoking. Studies of monozygotic and dizygotic twins suggest that the incidence of smoking in both twins is higher among the identical twin pairs, as well as continuance of the smoking habit. Animal models (mouse) of nicotine sensitivity indicate that approximately 35-40% of the variance in initial response to nicotine in different mouse strains is due to differences in the number and distribution of nicotinic receptors in the brain. Tolerance or addiction to nicotine in humans may, thus, be related to individual differences in the nicotinic acetylcholine receptor family. This gene family is complex and subunits are known to exist in variable combinations with different affinities for nicotine, differences which could relate to function in determining whether a person becomes addicted to tobacco use or not. The proposed studies will test the hypothesis that variability in nicotinic receptor expression or function exists in human postmortem brain and that these differences can be correlated with smoking history. We will measure the regional binding for the nicotinic receptor family in postmortem brain of smokers and non smokers, characterize the regional expression of mRNA for three nicotinic receptor subunits and determine the regional functional status of these receptors. Correlating results from this study with the subjects' smoking history in life, will provide new information concerning the importance of this receptor family in nicotine addiction.