期刊
NEUROIMAGE
卷 30, 期 4, 页码 1332-1339出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2005.11.014
关键词
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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 [F-18]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 (K-in(aPP)) in striatum, mesencephalon, and medial prefrontal cortex was calculated by volume-of-interest analysis. The macroparameter K-in(app) is a composite of several kinetic terms defining the distribution volume of FDOPA in brain (V-e(D)) and the relative activity of DOPA decarboxylase (k(3)(D)). Therefore, compartmental kinetic analysis was used to identify the physiological basis of the observed changes in K-in(aPP) period. The magnitude of K-in(aPP) was significantly increased in the putamen (18%) and mesencephalon (36%). Furthermore, V-e(D) in the brain was increased by 15%. Increments of k(3)(D) 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 k(3)(D) changes. (c) 2005 Elsevier Inc. All rights reserved.
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