Background and aims: D-amphetamine induced dopamine release displaces [F-18]fallypride at dopamine D2 receptors in extrastriatal areas as well as in the striatum (1). The objectives of the current study were to measure the test-retest reproducibility particularly in low density regions and the influences of dopamine depletion in addition to dopamine release on [F-18]fallypride binding by performing four PET scans in each healthy human subject: two baselines, one with amphetamine, and one with ?-methyl-para- tyrosine (AMPT) administration. Methods: Fourteen subjects participated in the study. Three participated in a pilot study with one baseline and one amphetamine scans. Eight participated in all four scans, and three had two baseline and one amphetamine scans. D-amphetamine (0.5 mg/kg) was administered orally 3 h before [F-18]fallypride injection. AMPT (43 mg/kg/day) was administered orally for 2 days. Equilibrium ratios of specific-to-nondisplaceable were measured using the Lammertsma's reference tissue model in caudate, putamen, thalamus, medial portion of orbitofrontal cortex, anterior cingulate, lateral and medial temporal cortices, substantia nigra, and colliculi. Except the initial three subjects, correlation was studied between amphetamine or AMPT-induced changes in [F-18]fallypride binding and performance in cognitive tests. Results: Test-retest variability and intraclass correlation coefficient (ICC) was 3.7 ? 7.7% and > 0.90, respectively, in all regions except anterior cingulate and colliculi which showed more than 10% variability and < 0.90 ICC. These two regions were excluded from further analyses. D-amphetamine displaced [F-18]fallypride significantly across the seven regions (p = 0.006) and in the five extrastriatal regions (p = 0.015) (Table). However, changes in individual regions reached to significant levels only in putamen and substantia nigra. AMPT did not cause significant changes in [F-18]fallypride binding, and there was no correlation between D-amphetamine and AMPT induced changes. Among cognitive tests, total number of words generated in Controlled Oral Word Association Test showed significant negative correlation with D-amphetamine induced decrease in [F-18]fallypride binding in thalamus and substantia nigra. Conclusions: The measurement of [F-18]fallypride binding showed excellent reproducibility even in extrastriatal regions. D-amphetamine induced dopamine release displaced [F-18]fallypride in both striatum and extrastriatal regions. However, the effects were weak showing correlation with cognitive measures only in thalamus, which is a relay center of information processing and substantia nigra, which may reflect overall dopamine release. There was no correlation in other regions, which may play more specific roles in cognitive function. These subjects who showed weak D-amphetamine effects did not show AMPT induced changes in [F-18]fallypride binding.
|Original language||English (US)|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|State||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine