INTRACELLULAR STUDY OF ETHANOL EFFECTS ON BRAIN NEURONS

本项目的总体目标是描述 乙醇（ETOH）对单个神经元电生理特性的影响 哺乳动物的大脑，并检查基本的离子机制， 对神经细胞膜的影响。这些研究的最终目的是 阐明ETOH如何改变中枢神经元的信息处理， 以了解人类使用ETOH期间大脑功能如何变化。 细胞内记录将用于研究ETOH对 蓝斑去甲肾上腺素能神经元和多巴胺能神经元 腹侧被盖区（VTA）的研究在大鼠脑切片。切片 (300μ）将被安装，完全浸没在记录室中。EtOH 将以已知的浓度在浴中或通过微压施加 弹射LC是大脑中最大的去甲肾上腺素能核团， 参与调节整体行为状态，例如：唤醒水平， 睡眠/觉醒、警觉水平和选择性注意。焦虑和 惊恐反应可能与LC功能亢进有关。这些 行为状态被ETOH改变，这会导致镇静，损害 选择性注意力，并具有抗焦虑作用。多巴胺能神经元 腹侧被盖区似乎在调节ETOH的奖赏效应中起重要作用 因此，在控制自愿的ETOH方面可能至关重要 摄入和滥用。ETOH，浓度在行为活性范围内 范围，导致LC神经元放电抑制，但增加放电 VTA神经元的比率。膜机制负责这两个 ETOH的不同作用将在一系列实验中进行检查 结合离子取代使用电流钳记录 以及使用特定的通道阻断剂。单电极电压钳将 用于识别受ETOH影响的特定膜电流。 关于急性ETOH作用机制的信息是必要的， 理解奖励机制的先决条件 ETOH的影响，以及ETOH耐受性和身体依赖性 开发.这反过来又应该允许合理发展 更好地治疗习惯性ETOH使用的治疗方案， ETOH戒断综合征。

The overall objective of this project is to describe the acute effects of ethanol (ETOH) on the electrophysiological properties of single neurons in the mammalian brain and to examine the basic ionic mechanisms which mediate these effects on neuronal membranes. The ultimate goal of such studies is to elucidate how ETOH alters information processing by central neurons in order to understand how brain function changes during human ETOH usage. Intracellular recording will be used to investigate ETOH effects on noradrenergic neurons of the locus coeruleus (LC) and dopaminergic neurons of the ventral tegmental area (VTA) studied in rat brain slices. Slices (300 mu) will be mounted, totally submerged in a recording chamber. ETOH will be applied in known concentrations in the bath or by micropressure ejection. The LC is the largest noradrenergic nucleus in the brain and is involved in regulation of overall behavioral state, such as: arousal level, sleep/wakefulness, level of vigilance and selective attention. Anxiety and panic reactions may be associated with hyperfunction of the LC. These behavioral states are altered by ETOH, which causes sedation, impairs selective attention and has an anxiolytic effect. Dopaminergic neurons of the VTA appear to be important in mediating the rewarding effects of ETOH and therefore may be of crucial importance in the control of voluntary ETOH intake and abuse. ETOH, in concentrations within the behaviorally active range, causes inhibition of firing of LC neurons but increases the firing rate of VTA neurons. Membrane mechanisms responsible for these two different actions of ETOH will be examined in a series of experiments employing current clamp recording in conjunction with ionic substitution and use of specific channel blockers. Single-electrode voltage clamp will be used to identify the specific membrane currents affected by ETOH. Information about the mechanisms of acute ETOH action is a necessary prerequisite to understanding the mechanisms underlying the rewarding effects of ETOH, as well as how ETOH tolerance and physical dependence develop. This, in turn, should permit the rational development of therapeutic regimens for better treatment of habitual ETOH usage and the ETOH withdrawal syndrome.