Tyrosine‐free amino acid mixture attenuates amphetamine‐induced displacement of [11C]raclopride in striatum in vivo: A rat PET study

Abstract
Previous neurochemical and behavioural studies show that tyrosine depletion using a nutritionally balanced tyrosine‐free amino acid mixture attenuates the dopamine‐releasing and psychostimulant properties of amphetamine. Here we investigate the effect of a tyrosine‐free amino acid mixture on striatal binding of [11C]raclopride, and amphetamine‐induced [11C]raclopride displacement, using positron emission tomography in the rat. Rats were scanned for 60 min after an i.v. injection of ∼11 MBq [11C]raclopride using a quad‐HIDAC system. Amphetamine (2 mg/kg i.p., 30 min prior to scan) caused a 12% reduction in [11C]raclopride distribution volume ratio (DVR) compared to saline‐injected controls. The tyrosine‐free amino acid mixture (1 g/kg i.p.) caused a small (+7%) but statistically insignificant increase in [11C]raclopride DVR and attenuated, although it did not fully block, the amphetamine‐induced reduction. These data are in keeping with previous neurochemical, immunocytochemical, and behavioural studies showing that tyrosine‐free amino acid mixtures reduce dopamine function and offer promise for future PET studies testing the effect of tyrosine‐depleting paradigms on dopamine release in humans. Synapse 51:151–157, 2004.