EM-TRANSMITTER INTERACTIONS OF STRIATAL OPIOID NEURONS

纹状体阿片神经元的电磁发射器相互作用

• 批准号: 3210342
• 负责人: VIRGINIA M PICKEL
• 金额: $ 17.85万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1997-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3210342
• 关键词: acetylcholine; afferent nerve; astrocytes; caudate nucleus; central neural pathway /tract; corpus striatum; developmental neurobiology; dopamine receptor; drug abuse; dynorphins; electron microscopy; endogenous opioid; enkephalins; experimental brain lesion; gamma aminobutyrate; histochemistry /cytochemistry; immunocytochemistry; in situ hybridization; laboratory rat; mature animal; neural plasticity; neurochemistry; neurons; neuropharmacology; neurotoxins; newborn animals; nucleus accumbens; putamen; radiotracer; sensorimotor system; sensory disorders; serotonin receptor; substantia nigra; synapses

Endogenous opiate peptides (enkephalins and dynorphin) within the dorsal (caudate-putamen nuclei, CPN) and ventral (nucleus accumbens septi) striatum have been implicated in motor and sensory responses to peripheral stimuli and in the rewarding properties of several drugs of abuse. These are most likely mediated by interactions between neurons containing endogenous opiates and transmitters in other neurons or afferents in compartmentally specific divisions of the dorsal and ventral striatum. In this competitive renewal, three studies are proposed that continue to investigate the cellular basis for functional interactions involving endogenous striatal opiates. Studies I and II will examine compartmentally specific subregions of dorsal and ventral striatum of normal adult rats using primarily combined immunogold-silver and immunoperoxidase labeling of two antibodies in single sections by electron microscopy (EM). Study I seeks to establish whether there is a cellular basis for functional interactions involving enkephalins and/or dynorphin and gamma-aminobutyric acid (GABA) or acetylcholine, two prominent transmitters in spiny and aspiny neurons. Study II seeks to determine (1) whether cortical or monoaminergic afferents terminate on neurons containing specific opiates, and/or (2) whether the neurons containing these opiates have other types of axonal associations with cortical or monoaminergic afferents that could mediate presynaptic modulation or dual regulation of common target neurons. Study III will use quantitative light microscopic immunocytochemical and in situ hybridization methods and morphometric EM-immunocytochemical analysis. The goal of this study is to determine whether neurons and/or astrocytes containing endogenous opiates, nerve growth factor, or S-100 protein show changes consistent with specific roles in plasticity of adult striatal cholinergic neurons or other afferents following neonatal neurotoxic lesions of dopaminergic neurons. The results from these three studies will provide basic science information relative to understanding how excitatory cortical afferents and monoaminergic afferents to the striatum modulate local circuits between neurons containing endogenous opiates and related transmitters in normal adult animals and in animals showing striatal compensation for neonatal dopamine depletion. The findings have implications for understanding mechanisms important for drug abuse, forebrain analgesia, and several motor and sensory disorders in humans.

内源性阿片类肽（Enkephalins和dynorphin） 背（尾状甲基核，CPN）和腹侧（核） 伏伏氏纹状体已与电机和 对外围刺激和奖励的感觉反应 几种滥用药物的特性。 这些很可能 由含有内源性的神经元之间的相互作用介导 其他神经元或传入中的鸦片和发射机 背侧和腹侧的特定特定区域 纹状体。 在这种竞争性更新中，三项研究是 提出的，继续研究细胞基础 涉及内源性纹状体鸦片的功能相互作用。 研究I和II将检查各个特定特定的子区域 正常成年大鼠的背侧和腹侧纹状体使用 主要组合免疫金 - 丝和免疫过氧化物酶 电子在单部分中标记两种抗体 显微镜（EM）。 研究我试图确定是否有 涉及Enkephalins的功能相互作用的细胞基础 和/或Dynorphin和γ-氨基丁酸（GABA）或 乙酰胆碱，两个突出的发射器，刺和asp。 神经元。 研究II旨在确定（1）是皮质还是 单胺能传入终止于包含特定的神经元 阿片类药物和/或（2）是否含有这些鸦片的神经元 具有其他类型的轴突关联与皮质或 单胺能传入可以介导突触前调节的传入 或对靶神经元的双重调节。 研究III将使用 定量光显微镜免疫细胞化学和原位 杂交方法和形态计量学EM-免疫细胞化学化学 分析。 这项研究的目的是确定神经元是否 和/或含有内源性鸦片，神经生长的星形胶质细胞 因子或S-100蛋白显示与特定一致的变化 成人纹状体胆碱能神经元的可塑性或 新生儿神经毒性病变后的其他传入 多巴胺能神经元。 这三项研究的结果将 提供有关理解的基础科学信息 激发性皮质传入和单胺能传入的传入 纹状体调节包含神经元之间的局部电路 正常成人的内源性鸦片和相关发射器 动物和表现出新生儿纹状体补偿的动物 多巴胺消耗。 这些发现对 了解对药物滥用重要的机制，前脑 镇痛，以及人类的几种运动和感觉障碍。