Examination of peptide neurotransmitters may lead to new insights in degenerative neurologic illnesses. The goals of this study are (1) to determine neuroanatomic pathways involving somatostatin in the basal ganglia, (2) to measure their relative contribution to the basal ganglia content of somatostatin-like immunoreactivity (SLI) as determined by radioimmunoassay (3) to study interactions between somatostatin and dopamine and its metabolites in the striatum and conversely the effects of dopamine blocking drugs on striatal SLI (4) to determine levels of somatostatin and other peptides in Parkinson's disease and to examine the normal distribution of somatostatin and other peptides within human basal ganglia (5) to measure somatostatin receptors in Huntington's disease and correlate this with the increased levels of SLI we have observed in basal ganglia in this illness. Somatostatin pathways within the basal ganglia will initially be examined by continuing our lesion studies followed by determination of striatal SLI in striatal punches by a specific radioimmunoassay. Specific pathways will be confirmed using fluorescence retrograde tracing combined with somatostatin immunocytochemistry. The interactions of dopamine and its metabolites with somatostatin will be examined using a push-pull cannula model. Dopamine, serotonin and their metabolites will be determined by high pressure liquid chromatography with electrochemical detection. The interactions of SLI with dopamine blocking drugs will be examined by administering these drugs to animals and subsequently measuring both SLI and catecholamines. Levels of SLI, substance P, neurotensin and enkephalin will be determined in both Parkinsonian brains and in detailed dissections of normal human brains. Somatostatin receptores will be analyzed in post-mortem tissue from Huntington's disease using a filtration assay with I125Tyr11 somatostatin as a tracer.
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