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1 Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden
Tyrosine-C14 was administered to nonanesthetized rats and mice by i.v. injection or constant-rate infusion during 20 min. The effect of chlorpromazine on the rates of accumulation and disappearance of labeled noradrenaline and dopamine was determined. After chlorpromazine the accumulation of dopamine-C14 in brain was increased up to 3-fold in both species. The effect was dose-dependent, was evident within 
hr after the drug administration and lasted for about 10 hr. Only in rats and only at the highest dosage used (25 mg/kg) was an increased accumulation of noradrenaline-C14 found. After chronic chlorpromazine treatment similar results were obtained. After prelabeling of the brain catecholamine stores by administration of tyrosine-C14, chlorpromazine significantly increased the rate of disappearance of dopamine-C14 but not that of noradrenaline-C14. The specific activity of tyrosine-C14 was not significantly altered by chlorpromazine. The results suggest that chlorpromazine accelerates synthesis and turnover of brain dopamine, possibly by blocking central dopamine receptors.
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