A kinetic study of the rate of formation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat: implications for the origin of DOPAC.

The rates of disappearance of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of rats treated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine were measured. Levels of dopamine. DOPAC and HVA in tissue were quantified in the striatum, nucleus accumbens and frontal cortex of the rat by means of high pressure liquid chromatography with electrochemical detection. Rats were sacrificed 1, 2 or 3 hr after the administration of alpha-methyl-p-tyrosine (200 mg/kg, i.p.). Levels of dopamine, DOPAC and HVA in tissue were logarithmically transformed, plotted against the duration of inhibition of tyrosine hydroxylase and the rate constant of the decline of dopamine and of its metabolites calculated. The rate constant of decline of DOPAC in each of brain studied was found to be greater than that for dopamine. The rate constant for the decline of dopamine was found to be greater in areas of the brain presenting the largest DOPAC/dopamine tissue ratios (frontal cortex greater than nucleus accumbens greater than striatum). The present results suggest that a substantial amount of DOPAC in brain derives from a newly formed pool of dopamine.