CELLULAR ASPECTS OF OPIOID NEUROTRANSMISSION

阿片肽完成的神经传递的某些方面， 它们的受体已经被彻底研究，因此可以作为 更普遍的肽能神经传递现象。尽管 在这些进展中，我们对阿片类药物的理解存在巨大差距， 神经传递是显而易见的。这些差距之一是缺乏 神经末梢之间的空间关系的知识， 含有阿片肽和具有阿片受体的膜。 第二个与此相关的差距是， 可能占据给定阿片样物质的内源性阿片样肽 受体亚型在给定的神经元回路在生理或 病理生理环境。 本文提出的研究的总体目标是表征 神经元元素之间的空间关系， 3个家族的阿片肽的神经元元件，其膜是 由克隆的阿片受体编码的蛋白质装饰， 非人类灵长类动物和人类大脑。这将通过追求来实现 三个具体目标： L.在区域一级确定 阿片肽和阿片受体的神经元储存部位 非人类灵长类动物大脑中的蛋白质。 2.在细胞水平上确定 阿片肽和阿片受体的神经元储存部位 在非人类灵长类动物大脑的选定区域的蛋白质。 3.确定阿片受体和肽在人体内 大脑以类似于猴子大脑的方式部署。 这些目标将通过建立一个综合地图集来实现 阿片肽及其受体在猴脑中的同步， 免疫荧光法。这本地图集将是独一无二的，因为它将 由共焦显微照片的平面蒙太奇组成， 解剖平面在尸检中获得的人脑的特定区域， 也将接受这一分析。超微结构研究， 免疫金技术将被用来澄清的空间安排 阿片肽和受体在猴子大脑的选定区域。 这些研究的图像将不仅以印刷品形式提供， 表格，但也有电子版，可随时通过 互联网

Some aspects of the neurotransmission accomplished by opioid peptides and their receptors have been thoroughly studied and thus serve as models of the more general phenomenon of peptidergic neurotransmission. In spite of these advances, large gaps in our understanding of opioid neurotransmission are apparent. One of these gaps is the lack of knowledge of the spatial relationships between nerve terminals that contain opioid peptides and the membranes that possess opioid receptors. A second, and related gap, is the lack of identification of the endogenous opioid peptides which are likely to occupy a given opioid receptor subtype in a given neuronal circuit under physiological or pathophysiological circumstances. The overall goal of the studies proposed herein is to characterize the spatial relationships between neuronal elements containing each of the 3 families of opioid peptides to neuronal elements whose membranes are decorated with the proteins encoded by the cloned opioid receptors in non-human primate and human brain. This will be accomplished by pursuit of 3 specific aims: l. Determine at a regional level the spatial relationships between neuronal storage sites of the opioid peptides and the opioid receptor proteins in non-human primate brain. 2. Determine at a cellular level the spatial relationships between neuronal storage sites of the opioid peptides and the opioid receptor proteins in selected regions of non-human primate brain. 3. Determine the extent to which opioid receptors and peptides in human brain are deployed in a manner similar to that found in monkey brain. These aims will be accomplished by construction of a comprehensive atlas of opioid peptides and their receptors in monkey brain by simultaneous, multicolor immunofluorescence. This atlas will be unique in that it will consist of planar montages of confocal micrographs in each of the three anatomical planes. Selected regions of human brain, obtained at autopsy, will also be subjected to this analysis. Ultrastructural studies using immunogold techniques will be used to clarify the spatial arrangements of opioid peptides and receptors in selected regions of monkey brain. Images from these studies will be made available not only in printed form, but also in an electronic version, readily accessible over the Internet.