This research proposal intends to elucidate the specific morphological substrate demonstrating the postsynaptic site of adenylate cyclase-linked mediation of dopaminergic neurotransmission in the rat caudate nucleus. The dopamine receptor subtype subserving cyclic AMP production has been termed the D1 receptor class. Utilization of histochemical techniques for in vitro receptor binding and immunohistochemistry cyclic AMP allows chemical determination of the element(s) mediating the response of this dopamine receptor subtype in highly organized tissue having multiple cell types. This approach will also allow correlation with other chemically defined cell populations of the caudate nucleus by neurotransmitter content, e.g., acetylcholinergic, GABAergic, substance P-containing, enkephalinergic, and somatostatin-containing. The receptor ligand-immunohistochemically characterized cell populations can be further correlated with their efferent destination through use of retrograde dye transport techniques. The ultrastructural study of synaptic relationships of the D1 dopamine receptor/cyclic AMP-containing cells will also be investigated. We plan to examine three experimental animal groups to demonstrate cellular changes which occur between 1) normal D1 receptor localization patterns, 2) the Parkinson-like, dopamine-lacking caudate nucleus, and 3) the dopamine-supplemented, nigrostriatal-lesioned rat. These investigations should further our understanding of dopaminergic mechanisms utilizing cyclic AMP second messenger systems in normal and neurochemically compromised states.
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