ETHANOL EFFECTS ON LOCUS COERULEUS & HIPPOCAMPAL NEURONS

乙醇对蓝斑的影响

• 批准号: 3445192
• 负责人: EMMANUEL Manuel LANDAU
• 金额: $ 4.14万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3445192
• 关键词: alcoholism /alcohol abuse; alpha adrenergic agent; alpha antiadrenergic agent; antihistamines; apomorphine; beta adrenergic agent; bromocriptine; calcium; calcium channel blockers; calcium metabolism; cimetidine; clonidine; cyclic AMP; cyclic GMP; cyproheptadine; dopamine; drug adverse effect; electrophysiology; ethanol; haloperidol; histamine; ion transport; isoproterenol; membrane permeability; membrane potentials; morphine; naloxone; neurons; neurotransmitters; nontherapeutic iontophoresis; norepinephrine; opiate alkaloid; potassium; sectioning; serotonin; serotonin inhibitor; synapses; yohimbine

Alcoholism is a major public health problem in the U.S.. Research into its interaction with the brain is far from conclusive. We propose to investigate the effects of ethanol on the locus coeruleus and on one of its major target areas, the hippocampus, because this system has been implicated in other types of addiction (opiates) and may have a major role in determining mood and modulating anxiety. Experiments will be conducted on tissue slices in vitro. Ethanol and other drugs will be introduced into the superfusing medium in known quantities. Iontophoretic and intracellular injection of drugs will also be done when indicated. Neurons will be impaled with glass micro-electrodes, and the membrane voltage amplified and measured, using standard electrophysiological techniques. Membrane resistance will be measured with a bridge arrangement and the cells will at times be voltage clamped using a one-electrode voltage clamp device. The slice will be stimulated directly to elicit synaptic potentials. We will be examining three major research questions: l) The effects of ethanol on the membrane properties and synaptic input characteristics of the neurons. These will include the membrane potential, membrane resistance, spike amplitude and threshold, the response to stimulation of synaptic inputs and the effects of bath applied transmitter substances; 2) The effects of ethanol on the calcium dependent potassium current, which is a major determinant of neuronal excitability. We will attempt to elucidate how ethanol interacts with intracellular calcium and cyclic nucleotides to affect this current; 3) The effects of ethanol will be compared with a number of membrane fluidizing agents to test the hypothesis that membrane fluidization is the molecular mechanism of action of ethanol.

酒精中毒是美国的主要公共卫生问题。 与大脑的互动远非结论性。 我们建议 研究乙醇对基因座的影响及其其中一种 主要目标区域，海马，因为该系统已经 与其他类型的成瘾（鸦片）有关，可能具有重要作用 在确定情绪和调节焦虑时。 将进行实验 在体外切片上。 乙醇和其他药物将被引入 已知数量的超级培养基。 离子遗漏和 指示时还将进行细胞内注射药物。 神经元 将用玻璃微电极和膜电压刺穿 使用标准电生理技术进行放大和测量。 膜电阻将通过桥梁布置测量 有时将使用单电压电压夹夹具电压 设备。 切片将直接刺激以引起突触 潜力。 我们将研究三个主要研究问题：l） 乙醇对膜特性和突触输入的影响 神经元的特征。 这些将包括膜电位， 膜电阻，尖峰振幅和阈值，对 刺激突触输入和浸泡发射机的影响 物质； 2）乙醇对钙依赖钾的影响 电流，这是神经元兴奋性的主要决定因素。 我们将 试图阐明乙醇如何与细胞内钙相互作用和 环状核苷酸影响该电流； 3）乙醇的影响将 与许多膜流化剂进行比较以测试 假设膜流化是分子的作用机理 乙醇。