ETHANOL EFFECTS IN CNS TISSUE IN LAS AND HAS RATS

对调节行为的神经机制的理解 乙醇的作用是理解酒精的关键 醉酒、酗酒和酗酒。世界经济一体化的影响 去甲肾上腺素能神经支配对神经功能的调节作用 应激或压力引起的神经元对乙醇反应的改变 唤醒，以及个体在神经元方面的表型 乙醇敏感性及其对神经元乙醇效应的调节作用 中枢交感神经元可能会影响个体的 在这些行为状态下对酒精的反应和滥用。这个 拟议的研究将集中在LAS和HAS老鼠上，这些老鼠是遗传的 表现与酒精有关的行为的不同变体，如 研究急性乙醇与乙醇相互作用的模型系统 神经递质作用于小脑中的去甲肾上腺素和GABA，以及 对这些影响的快速急性神经元耐受(RANT)。的影响 酒精暴露对哺乳动物中枢神经系统功能的影响 使用动作电位活动的细胞外记录进行追踪 单神经元、全细胞膜片钳记录GABAA/C1通道 功能和体内电化学监测突触前释放 以及对去甲肾上腺素和其他单胺的摄取。录音将会是 在大鼠体内和体外脑片中进行，以及药物 和传递体将通过途径激活、灌流(in 体外)、全身给药(体内)和局部给药 来自多管微吸管的细胞微环境。长的- 这项研究计划的学期目标有三个方面。第一，要 确定与行为相关的神经元酒精活动 酒精敏感性培育成LAS，并有大鼠。第二，到 描述这些乙醇作用的机制。第三，到 描述神经元对乙醇反应的变化，以及 神经递质系统功能的改变，发生 通过RANT的诱导，探讨其神经机制。 并确定这一现象在机制中的作用 对酒精高度敏感。本项目期的具体目标 主要研究内容如下：1)探讨神经元无水乙醇的假说 小脑的敏感度和咆哮与行为有关 表型。2)确定小脑对乙醇的反应是否 通过b-肾上腺素能机制的脱敏来调节。3)学习 小脑儿茶酚胺突触的突触前作用

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.