CELLULAR ASPECTS OF OPIOID NEUROTRANSMISSION

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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.