No effect of α-methyl-para-tyrosine-induced dopamine depletion on [¹⁸F]fallypride binding in healthy humans who showed D-amphetamine-induced displacement

Abstract

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Objectives: Amphetamine (Amphet)-induced dopamine (DA) release displaces [¹⁸F]fallypride (FAY) at DA D2 receptors in extrastriatal areas as well as in striatum (Riccardi Neuropsychopharmacol 2006;31:1016). In striatum, phasic DA release is regulated by the tonic release (Grace Neuroscience. 1991;41:1).The objectives of the this study were to measure the test-retest reproducibility and the influences of DA depletion in addition to DA release on FAY binding by performing four PET scans in each healthy human subject: two baselines, one with Amphet, and one with α-methyl-para-tyrosine (AMPT) administration. Methods: Amphet (0.5 mg/kg) was administered orally 3 h before FAY injection (n=14). AMPT (43 mg/kg/day) was administered orally for 2 days (n=8). Binding potential was measured using the Lammertsma's reference tissue model in the regions shown in the table. Correlation was studied among Amphet- and AMPT-induced changes in FAY binding and performance in cognitive tests. Results: Test-retest variability was 3.7 – 7.7% in all regions. Amphet displaced FAY 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 (SN). AMPT did not cause significant changes in FAY binding, and there was no correlation between Amphet- and AMPT-induced changes. Among cognitive tests, total number of words generated in the Controlled Oral Word Association Test showed significant negative correlation with Amphet-induced decrease in FAY binding in thalamus and SN. Conclusions: The measurement of FAY binding showed excellent reproducibility. Despite small but significant effect of Amphet-induced DA release on FAY binding in both striatum and extrastriatal regions, AMPT did not change the binding. Effect of DA levels on FAY binding is limited, and more complete depletion paradigm is required to study baseline DA levels.

Research Support (if any): NIMH Z01-MH-002795-04

Amphetamine-induced changes (%) in [¹⁸F]fallypride binding