Abstract

Several lines of evidence now suggest that inhibition of firing in the nigro-neostriatal dopamine system is followed by an immediate and rapid increase in the rate of dopamine synthesis in the neostriatum. A similar phenomenon is not observed in the norepinephrine or serotonin systems in brain. The increase in synthesis appears to take place at the tyrosine hydroxylase step. Although the synthesis of dopamine returns to normal after dopamine levels have been increased, the elevated dopamine levels do not have a further inhibitory effect on tyrosine hydroxylase activity. Pretreatment with dopamine agonists such as 1-(2-pyrimidyl)-piperonyl-piperazine (ET495) or apomorphine prevents the increase in dopamine synthesis normally observed after inhibition of impulse flow. One possible explanation for these phenomena may be found in the hypothesis that a presynaptic receptor on the dopamine terminal may be involved in the regulation of dopamine synthesis and storage.