Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers after acute haloperidol challenge

In animal studies, acute antipsychotic treatment was shown to enhance striatal DOPA-decarboxylase (DDC) activity. However, this phenomenon has not been demonstrated in humans by positron emission tomography (PET). Therefore, we investigated acute haloperidol effects on DDC activity in humans using [18F]fluorodopa (FDOPA) PET. Nine healthy volunteers were scanned with FDOPA in drug-free baseline conditions and after 3 days of haloperidol treatment (5 mg/day). A continuous performance test (CPT) was administered in both conditions. The net blood–brain clearance of FDOPA (Kinapp) in striatum, mesencephalon, and medial prefrontal cortex was calculated by volume-of-interest analysis. The macroparameter Kinapp is a composite of several kinetic terms defining the distribution volume of FDOPA in brain (VeD) and the relative activity of DOPA decarboxylase (k3D). Therefore, compartmental kinetic analysis was used to identify the physiological basis of the observed changes in Kinapp period. The magnitude of Kinapp was significantly increased in the putamen (18%) and mesencephalon (36%). Furthermore, VeD in the brain was increased by 15%. Increments of k3D in the basal ganglia did not attain statistical significance. The significant worsening of CPT results did not correlate with changes in FDOPA utilization. The present PET results indicate potentiation of FDOPA utilization in human basal ganglia by acute haloperidol treatment, apparently due to increased availability throughout the brain. The stimulation of DDC cannot be excluded due to insufficient statistical power in the estimation of k3D changes.