We propose to study the function of dopamine (DA) in schizophrenia, both at baseline and after a pharmacological challenge. 1)We will use D-amphetamine to increase DA in the synapse. By enhancing DA, we will decrease [123I]IBZM binding to the D2 receptors. 2) We willl use alpha-methyl-para-tyrosine, (AMPT), to decrease DA concentration. By depleting DA, we will increase [123I]IBZM binding to the D2 receptors. This protocol will provide in two scans a complete characterization of dopaminergic function in 45 patients with schizophrenia compared to 45 matched healthy controls. All subjects will be scanned twice, at two day interval. A first SPECT scan will include a D-amphetamine challenge and will be followed by oral administration of AMPT (1000mg q 6 h) for 48 h, for a total dose of 8 g per subject. A second scan will be performed after AMPT administration. We will compare D-amphetamine induced DA release and AMPT induced DA depletion between patients with schizophrenia compared to healthy controls.
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