ETHANOL EFFECTS IN CNS TISSUE IN LAS AND HAS RATS

了解神经元机制介导的行为 乙醇的影响对于理解酒精至关重要 醉酒、酗酒和酒精中毒。 的影响 去甲肾上腺素能神经支配对神经元功能的影响可能是调节 神经元对乙醇反应性的改变，例如应激或 唤醒，以及个体在神经元方面的表型 对乙醇的敏感性和神经元乙醇效应的调节 中枢交感神经元可能会影响一个人的 对酒精的反应和滥用。 的 拟议的研究将集中在LAS和HAS大鼠，这是遗传 差异表现出酒精相关行为的变体，如 一个模型系统，用于检查急性乙醇相互作用， 小脑中的神经递质作用去甲肾上腺素和GABA，以及 快速急性神经元耐受（RANT）。 的影响 乙醇暴露对哺乳动物中枢神经系统功能的影响 使用细胞外记录的动作电位活动， 单个神经元，全细胞膜片钳记录GABAA/C1通道 功能和体内电化学来监测突触前释放 以及去甲肾上腺素和其他单胺的摄取。记录将 在体内大鼠脑和体外脑切片中进行， 和发射器将通过通路激活、灌流（in 体外）、全身给药（体内）和局部给药。 从多管微量移液器的细胞的微环境。 很长的- 该研究计划的长期目标有三个方面。 一是 识别与行为相关的神经元乙醇作用， 乙醇敏感性繁殖到LAS和HAS大鼠中。二是 描述这些乙醇作用的机制。三是 表征神经元对乙醇反应的变化，以及 神经递质系统功能的改变， 通过RANT的诱导，探讨其神经机制， 变化，并确定这种现象的作用机制， 急性酒精敏感性本项目期间的具体目标 主要内容如下：1）探讨神经元乙醇 小脑中的敏感性和RANT与行为相关 表型2)为了确定小脑中的RANT转化为EtOH是否 由β-肾上腺素能机制的脱敏介导。 3)研究 小脑儿茶酚胺突触在RANT中的突触前作用

An understanding of neuronal mechanisms which mediate the behavioral effects of ethanol is critical to the understanding of alcohol intoxication, alcohol abuse, and alcoholism. The influences of the noradrenergic innervation on neuronal function may well regulate alterations in neuronal responsiveness to ethanol with e.g. stress or arousal, and the phenotype of the individual in terms of neuronal sensitivity to ethanol and regulation of neuronal ethanol effects by central sympathetic neurons will likely influence an individual's response to, and abuse of, alcohol in those behavioral states. The proposed studies will focus on LAS and HAS rats, which are genetic variants that differentially manifest an alcohol-related behavior, as a model system for examining acute ethanol interactions with neurotransmitter actions norepinephrine and GABA in the cerebellum, and rapid acute neuronal tolerance (RANT) to those effects. The effects of ethanol exposure on mammalian central nervous system function will be pursued using extracellular recordings of action potential activity of single neurons, whole-cell patch clamp recordings GABAA/C1 channel function, and in vivo electrochemistry to monitor presynaptic release and uptake of norepinephrine and other monoamines. Recordings will be carried out in rat brain in vivo and in brain slices in vitro, and drugs and transmitters will be applied by pathway activation, superfusion (in vitro), systemic administration (in vivo) and locally to the microenvironment of the cell from multibarrel micropipettes. The long- term objectives of this research program are three fold. First, to identify neuronal ethanol actions that are relevant to the behavioral ethanol sensitivities bred into LAS and HAS rats. Second, to characterize the mechanisms of these ethanol actions. Third, to characterize changes in neuronal responses to ethanol, as well as alterations in the function of neurotransmitter systems, which occur with the induction of RANT, explore the neuronal mechanisms of those changes and to determine the role of this phenomenon in the mechanisms of acute ethanol sensitivity. The specific aims for this project period are as follows: 1) To investigate the hypothesis that neuronal EtOH sensitivity and RANT in the cerebellum are behaviorally relevant EtOH phenotypes. 2) To determine if RANT to EtOH in the cerebellum is mediated by a desensitization of b-adrenergic mechanisms. 3) To study the presynaptic role of cerebellar catecholamine synapses in RANT.