This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This study proposes to develop new methods for measuring d-amphetamine induced dopamine (DA) release and baseline extracellular levels of DA in the thalamus, limbic regions, substantia nigra, and cortex in man. A considerable body of literature indicates that dopaminergic neurotransmission in these regions is centrally involved in the pathophysiology of schizophrenia, psychostimulant drug abuse, and attention deficit disorder. At present there are no methods available for measuring DA release or baseline extracellular DA levels in these regions. We have developed [18F) fallypride as a high affinity PET radioligand for the DA D2 receptor with sensitivity to extracellular DA levels. The hypotheses of this study follows:1) D-amphetamine (0.43mg/kg p.o.) released DA will produce a 10-15 percent decrease in the binding potentials of [18F] fallypride in extrastriatal brain regions, e.g. thalamus, limbic regions and cortex as well as in striatum in man.2) DA depletion with alphamethylpartyrosine (AMPT, 71.4 mg/kg over 26 hours) will produce an increase of about 10-12 percent in the [18F] fallypride binding potentials in extrastriatal regions, and schizophrenia in man.The achievement of these hypotheses will allow the use of PET [18F] fallypride studies prior to and following either d-amphetamine or AMPT as methods for measuring DA release or baseline extracellular DA levels in extrastriatal brain regions in man.
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