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 将使用细胞外记录的行动， 来自单个神经元的潜在活动以及诱发电位，以及 细胞内记录膜特性。 录音将被携带 在体内，在完整的大脑原位，在多个大脑移植在oculo， 在脑切片和脱离的眼内脑移植物中， 体外 除了研究酒精对啮齿动物大脑的影响外， 将研究乙醇对人类神经元的作用， 异种移植 研究将集中在遗传变异， 不同的酒精相关行为作为模型系统， 乙醇的作用，以及研究乙醇的依赖性和戒断。 我们的方法是使用遗传和药理学技术， 独立操纵行为效应和神经元的行动， 乙醇 我们目前最感兴趣的是乙醇与 去甲肾上腺素、多巴胺、兴奋性氨基酸和GABA 蓝斑、海马和小脑。 我们建议扩展这些研究 多巴胺能腹侧被盖区及其靶区。 很长的- 该研究计划的长期目标有三个方面。 第一、 将使用电生理学和体内电化学技术 这两种方法都将急性神经元对乙醇的反应表征为直接膜反应， 影响，与突触输入的调节相互作用，或 神经元通路的活动。 第二，神经元反应的变化 以及神经递质系统的功能变化， 在诱导乙醇依赖和戒断后确定。 最后，使用选择性繁殖和转基因遗传变异，乙醇- 诱导的电生理反应将与酒精相关， 诱导行为。 更深入地了解乙醇如何改变CNS 功能应该为酒精问题提供新的见解 中毒和酗酒。

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.