The overall goal of this proposal is to determine the synaptic circuitry of opioid systems in the normal adult stiatum and in the striatum of adult animals having unilateral removal of their dopaminergic afferents at 3 days after birth. The first study is focused on the synaptic relationships between: (1) dopaminergic afferents from the substantia nigra and intrinsic striatal neurons containing the opioid peptides, (Met5- and Leu5-enkephalin), gamma-aminobutyric acid (GABA), and the acetylcholine synthesizing enzyme, choline acetyltransferase (CAT), (2) cholinergic neurons and medium spiny neurons containing opioid peptides or GABA, (3) somatosensory cortical afferents and neurons containing opioid peptides, GABA, or acetylcholine. The second study proposes to address the issues of whether removal of dopaminergic afferents by 6-hydroxydopamine in the early postnatal period alters the regional densities of immunoreactivity for the opioid peptides or other transmitters; the density or distribution of somatosensory cortical afferents; or the ultrastructural morphology of target dendrites in the mature striatum. The primary methods include light and electron microscopic immunocytochemistry using peroxidase and iodinated markers for single and dual labeling of antisera in single sections of rat caudate nuclei. The results from the two studies should broaden our knowledge of synaptic interactions between neurons containing immunoreactivity for opioid peptides and other GABAergic or cholinergic striatal neurons and their relation to afferents from the substantia nigra and somatosensory cortex. This information may be important for: (1) understanding the synaptic relationships of forebrain opioid neurons which underlie certain actions of narcotic analgesics and (2) further understanding the etiology and developing improved therapeutic measures for sensory symptoms in Parkinson's disease and other clinical disorders.
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