In vivo estimation of tyrosine hydroxylation in the dopaminergic terminals of the rat neostriatum

Abstract

Abstract An approach has been developed to distinguish dopamine synthesis from its release and utilization in dopamine terminals of the rat neostriatum (NCP). It enables a direct in vivo estimation of tyrosine hydroxylation, a rate limiting step in dopamine synthesis. Locally injected l-3,5[3H]tyrosine is converted to [3H]dopamine in the NCP. The conversion of the labelled tyrosine into [3H]dopa leads to local accumulation of [3H]water (3H-H2O). The initial accumulation (3 min) of the 3H-H2O levels in tissues gives a good reflection of the rate of tyrosine hydroxylation occurring in the dopamine terminals of the nigro-striatal pathway. In effect, 3H-H2O formation (1) disappeared after elective degeneration of the nigro-neostriatal dopamine neurons, (2) was inhibited by α-methyl-p-tyrosine, (3) was not affected by intraperitoneal injection of urea, which is known to reduce brain water content, (4) moreover, 3H-H2O accumulation was enhanced by various neuroleptic drugs and inhibited by (+)-amphetamine. Finally, Ro 4–4602 an inhibitor of dopa-decarboxylase reduced 3H-H2O formation 30 min after its injection.