GENETIC APPROACHES TO NEUROPHARMACOLOGY OF ETHANOL

科罗拉多大学酒精研究中心的重点是 使用遗传学方法来阐明神经药理学机制， 乙醇会对中枢神经系统产生作用。 使用 远系繁殖动物的遗传选择，对乙醇的行为反应 提供了一种独特的工具， 采取这些应对措施。 现在有可用的远系小鼠品系，其对短睡眠-SS）或 敏感（长睡眠LS）的急性作用的乙醇和其他线路， 接受酒精（HA）或拒绝酒精（LA）。 我们现在选择性地繁殖 小鼠对乙醇的高或低成瘾性。 遗传和生物化学工具被用来研究乙醇对 神经递质的合成、功能和代谢 的中心。 前房脑移植术的临床应用 大鼠眼，神经递质的密度和性质测定 受体，与神经递质合成相关的酶的动力学， 降解以及行为研究被广泛采用。 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 在人类和低等动物中发育中的胎儿（胎儿酒精综合征）将 被研究。 为了研究乙醇代谢对中枢神经系统的影响， 行动，采取了几种方法。 我们研究了几个 抑制或引起诱导乙醇和醛代谢的化合物。 我们还确定了生物活性代谢产物的结构， 用气相色谱-质谱法测定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.