GENETIC APPROACHES TO NEUROPHARMACOLOGY OF ETHANOL

科罗拉多大学酒精研究中心的重点是 用遗传学方法阐明神经药理学机制 乙醇对中枢神经系统产生作用。对.的使用 因对乙醇的行为反应而从基因上选择的远缘杂交动物 提供了一种独特的工具来关联神经化学和神经生理学 采取这些应对措施。 现在有可用的近交系小鼠，它们抵抗短睡眠-SS)或 对乙醇和其他物质的急性作用敏感(长睡眠LS) 接受酒精(HA)或拒绝酒精(LA)。我们现在正在有选择地繁殖 小鼠对乙醇的成瘾性高或低。 遗传和生化工具被用来研究乙醇对人的影响 多个实验室的神经递质合成、功能和代谢 中心的一部分。前房脑移植的技术探讨 大鼠眼部神经递质密度和性质的测定 受体，与神经递质合成相关的酶的动力学和 退化和行为研究被广泛使用。的研究 乙醇膜相互作用是这些研究的主要组成部分， 与神经递质研究相关。乙醇对人血清白蛋白的影响 在人类和低等动物身上发育的胎儿(胎儿酒精综合征)将 被研究。 为了研究乙醇的代谢对其中枢的影响。 行动，采取了几种办法。我们研究了几个 抑制或诱导乙醇和乙醛代谢的化合物。 我们还测定了其生物活性代谢物的结构。 通过气相色谱-质谱法改变行为或酶活性的化合物 光谱技术。

The focus of the Alcohol Research Center at the University of Colorado is on the use of genetic methods to elucidate the neuropharmacological mechanisms by which ethanol brings about its actions on the central nervous system. The use of outbred animals genetically selected for behavioral responses to ethanol provides a unique tool to correlate the neurochemical and neurophysiological measures with these responses. There are now available outbred mice lines that are resistant short sleep-SS) or sensitive (long-sleep LS) to the acute action of ethanol and other lines that accept alcohol (HA) or reject alcohol (LA). We are now selectively breeding mice for high or low addictability to ethanol. The genetic and biochemical tools are used to study the actions of ethanol on neurotransmitter synthesis, function and metabolism in a number of laboratories of the Center. Techniques of brain transplantation to the anterior chamber of the eye of rats, measurement of density and properties of neurotransmitter receptors, kinetics of enzymes associated with neurotransmitter synthesis and degradation as well as behavioral studies are employed extensively. Studies of ethanol membrane interactions is a major component of these studies and is correlated with the neurotransmitter studies. The effect of ethanol on the developing fetus (fetal alcohol syndrome) in both humans and lower animals will be studied. In order to study the influence of the metabolism of ethanol on its central actions, several approaches are taken. We study the actions of several compounds which inhibit or cause induction of ethanol and aldehyde metabolism. We also determine the structure of the biologically active metabolites of compounds which alter behavior or enzyme activities by gas-chromatography-mass spectrometric techniques.