ETHANOL EFFECTS ON CNS TISSUE IN VIVO & IN VITRO

乙醇暴露对哺乳动物中枢神经系统的影响 使用两种细胞外动作记录来追求功能 单个神经元的电位活动以及诱发电位，以及 膜特性的细胞内记录。录音将会随身携带 在活体内，在完整的大脑中，在眼球中，在多个脑移植中， 在脑片中以及在分离的眼内脑移植中 体外培养。除了研究酒精对啮齿类动物大脑的影响外，我们还 将研究酒精对人脑中使用的神经元的作用 异种移植物。研究将集中在遗传变异上。 以差异酒精相关行为为模型系统研究急性酒精中毒 酒精的作用以及研究酒精依赖和戒断。 我们的方法是利用遗传和药理学技术 独立操控的行为效应和神经动作 乙醇。我们目前最感兴趣的是乙醇与 基因座中的去甲肾上腺素、多巴胺、兴奋性氨基酸和GABA 蓝斑、海马体和小脑。我们建议扩大这些研究的范围 多巴胺能腹侧被盖区及其靶区。长的- 这项研究计划的学期目标有三个方面。第一, 将使用电生理和体内电化学技术 两者均以乙醇为直接膜表征急性神经元反应 影响，与突触输入的调制相互作用，或改变 神经通路的活动。第二，神经元反应的变化 酒精，以及神经递质系统的功能变化，将 在诱导酒精依赖和戒断后确定。 最后，使用选择性培育和转基因的遗传变异，乙醇- 诱发的电生理反应将与酒精相关- 诱导性行为。对乙醇如何改变中枢神经系统有更深入的了解 函数应该为酒精问题提供新的见解 醉酒和酗酒。

The effects of ethanol exposure on mammalian central nervous system function will be pursued using both extracellular recording of action potential activity from single neurons as well as evoked potentials, and intracellular recording of membrane properties. Recordings will be carried out in vivo in the intact brain in situ, in multiple brain grafts in oculo, and in brain slices as well as in extricated intraocular brain grafts in vitro. In addition to our studies of ethanol effects in rodent brain, we will study ethanol actions on human neurons using in oculo brain xenografts. Studies will focus on genetic variants manifesting differential alcohol-related behaviors as model systems for examining acute ethanol actions as well as for studying ethanol dependence and withdrawal. Our approach is to use genetic and pharmacological techniques to independently manipulate the behavioral effects and neuronal actions of ethanol. We are currently most interested in ethanol interactions with norepinephrine, dopamine, excitatory amino acids, and GABA in locus coeruleus, hippocampus and cerebellum. We propose to extend these studies to the dopaminergic ventral tegmental area and its target areas. The long- term objectives of this research program are three fold. First, electrophysiological and in vivo electrochemical techniques will be used both to characterize acute neuronal responses to ethanol as direct membrane effects, modulatory interactions with synaptic inputs, or alterations in the activity of neuronal pathways. Second, changes in neuronal responses to ethanol, as well as functional changes in neurotransmitter systems, will be determined after induction of ethanol dependence and withdrawal. Finally, using selectively bred and transgenic genetic variants, ethanol- induced electrophysiological responses will be correlated with alcohol- induced behaviors. A greater understanding of how ethanol alters CNS function should furnish new insights into the problems of alcohol intoxication and alcoholism.