This is a sharply focused interdisciplinary, interdepartmental Program Project Grant. All of the proposed research is directed toward in vivo localization of neuro-receptors. Co-investigators include members of our faculty from Pharmacology and Experimental Therapeutics, Neurotoxicology, Neurology, Neurosurgery, Psychiatry, Radiology and Nuclear Medicine (all of The Johns Hopkins Medical Institutions) and the Graduate Chemistry Department of The Johns Hopkins University. The current research is focused on in vivo localization of the dopamine and opiate receptors. Initial research will be directed toward: 1) Rapid """"""""on line"""""""" synthesis of 11C spiroperidol (a dopamine receptor specific binding agent) and 11C diprenorphine (an opiate receptor specific binding agent), and 2) An evaluation of this total system in a variety of animal models, prior to beginning studies in man. Thereafter we will concentrate on studies of those dopamine and opiate receptors in appropriate disease states (including Parkinsonism, Huntington's Disease, Tardive Dyskinesia, Schizophrenia, chronic pain patients, etc.). In addition we will use standardized methods for measurement of regional cerebral blood flow, blood volume and metabolism where indicated in these patients. We believe the ability to study non-invasively such neuroreceptors in man will lead to fundamentally important new information, and provide, in some instances, improved approaches to therapy.
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