CELLULAR/MOLECULAR MECHANISMS UNDERLYING NEUROADAPTATION TO CHRONIC ALCOHOL

这些关于酒精对中枢神经系统神经元作用的持续研究将 确定长期接触酒精是否会产生长期的适应性 参与兴奋性突触传递的细胞通路的变化。 酒精对细胞内至关重要的突触功能的影响 并将研究神经元间的通信，包括：(A) 突触输入启动的细胞内钙信号，(B)神经类固醇 突触传递和长时程增强(LTP)的调制，以及 (C)发射机之间的相互作用。这些突触功能将被评估 在三种情况下：(A)对照基线，(B)长期饮酒后 (C)戒酒一段时间后。一种比较 结果将揭示酒精诱导的这些突触的变化 功能和变化的相对永久性。各种策略 将被用来识别酒精的细胞位置和机制 行动。要研究的主要递质是谷氨酸，它的作用 通过NMDA受体。酒精对阿片受体相关钙离子的作用 还将评估信令。来自两个大脑区域的神经元， 海马体和杏仁体，将被研究。已知这两个大脑区域 卷入酒精对行为的影响。《公约》的具体目标 研究内容如下：(1)研究慢性酒精对健康的影响。 突触输入激活并相互关联的细胞内钙信号事件 谷氨酸和阿片受体，并确定慢性酒精 诱导受体连接的钙信号通路的长期变化， 都是在禁欲期间维持的。(2)确定是否 神经类固醇对兴奋性突触传递和LTP的调节作用 被酒精治疗模式改变，产生依赖和 动物模型中的禁欲。(三)建立鼠类养殖模式 研究酒精对突触系统影响的杏仁核神经元 被认为与上瘾行为直接相关的。体外培养 切片制剂将用于这些研究，因为它们提供了 电生理和显微钙离子的技术优势 要使用的成像技术。这些研究的结果将有助于 对了解由大鼠脑缺血引起的神经适应性改变有重要意义。 在酒精依赖和戒酒的情况下饮酒，并可 揭示一般原则，将有助于理解 酒精作用的基本神经机制正在研究中 TSRI-ARC的其他组件。

These continuing studies of alcohol's actions on CNS neurons will determine if chronic exposure to alcohol produces long-lasting adaptive changes in cellular pathways involved in excitatory synaptic transmission. Alcohol's effects on synaptic functions that are critical to intracellular and interneuronal communication will be examined including: (a) intracellular Ca2+ signaling initiated by synaptic input, (b) neurosteroid modulation of synaptic transmission and long-term potentiation (LTP), and (c) transmitter interactions. These synaptic functions will be assessed under three conditions: (a) control baseline, (b) after chronic alcohol exposure and, (c) after a period of alcohol abstinence. A comparison of results will reveal alcohol-induced alterations in these synaptic functions and the relative permanence of the changes. Various strategies will be used to identify the cellular sites and mechanisms of alcohol action. The main transmitter to be studied is glutamate, and its actions via the NMDA receptor. Alcohol's action on opiate receptor-linked Ca2+ signaling will also be assessed. Neurons from two brain regions, the hippocampus and amygdala, will be studied. Both brain regions are known to be involved in the behavioral effects of alcohol. The Specific Aims of the studies are: (1) to investigate effects of chronic alcohol on intracellular Ca2+ signaling events activated by synaptic input and linked to glutamate and opiate receptors, and to determine if chronic alcohol induces long-term changes in receptor-linked Ca2+ signaling pathways that are maintained during abstinence from school. (2) To determine if neurosteroid modulation of excitatory synaptic transmission and LTP is altered by alcohol treatment paradigms that produce dependence and abstinence in animal models. (3) To establish a rodent culture model of amygdala neurons for studies of alcohol's effects on synaptic systems thought to be directly involved in addictive behavior. In vitro culture and slice preparations will be used for these studies because they offer technical advantages for the electrophysiological and microscopic Ca2+ imaging techniques to be used. Results from these studies will contribute significantly to an understanding of the neuroadaptive changes induced by alcohol under conditions of alcohol dependence and abstinence, and may reveal general principles that will contribute to an understanding of the basic neuronal mechanisms underlying alcohol's actions being studied in other components of the TSRI-ARC.