In the present protocol, dopaminergic function will be directly examined in schizophrenic patients and healthy controls by estimating synaptic dopamine concentrations through amphetamine-induced displacement 11-C-raclopride (RAC) with PET. Raclopride, a highly specific D-2 ligand, competes with synaptic dopamine for D-2 receptor binding. By increasing synaptic dopamine concentrations with amphetamine, thereby decreasing the amount of bound radiotracer, an estimate of synaptic dopamine concentration is derived. We have completed nonhuman primate studies which validated the amphetamine/raclopride methodology. We found that a constant infusion of RAC in a single study had a number of advantages over a two-scan bolus approach (Carson et al 1995); amphetamine (.4mg/kg) produced 18% (mean, N=5) RAC displacement (Carson et al 1995); and there was a good relationship between RAC displacement and simultaneaously-derived extracellular dopamine levels (Breier et al 1995: Breier et al 1995). Our normal volunteer studies (N=12) demonstrate 15% RAC displacement (Breier et al 1995) and have addressed methodologic issues such as the effects of movement and nonspecific effects of """"""""nondopaminergic"""""""" psychotogenic agents (e.g., ketamine). We have completed scanning 11 schizophrenia patients (5 neuroleptic-naive and 6 neuroleptic withdrawn) and found they have significantly greater amphetamine-induced RAC displacemtn than controls (Breier et al. 1996). These data support the dopamine overactivity hypothesis of schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002693-02
Application #
2578823
Study Section
Special Emphasis Panel (ETB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1996
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code