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.
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