Tyrosine-free amino acid mixture attenuates amphetamine-induced displacement of [11C]raclopride in striatum in vivo: a rat PET study.
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 [(11)C]raclopride, and amphetamine-induced [(11)C]raclopride displacement, using positron emission tomography in the rat. Rats were scanned for 60 min after an i.v. injection of approximately 11 MBq [(11)C]raclopride using a quad-HIDAC system. Amphetamine (2 mg/kg i.p., 30 min prior to scan) caused a 12% reduction in [(11)C]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 [(11)C]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.
Le Masurier
Marisa
M
University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK.
Houston
Gavin
G
Cowen
Philip
P
Grasby
Paul
P
Sharp
Trevor
T
Hume
Susan
S
D000596:Amino Acids / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D008297:Male; D023421:Models, Animal; D020891:Raclopride / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed; D014443:Tyrosine / Q000378:metabolism*
D000596:Amino Acids; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D014443:Tyrosine; D020891:Raclopride; D000661:Amphetamine