Changes in Neostriatal Dopamine Concentrations in Response to Levodopa Infusions

Abstract: Levodopa was infused under various circumstances of pretreatment into the ear veins of unanesthetized rabbits. Concentrations of neostriatal dopamine formed in response to levodopa administration were determined. The aim was to characterize the temporal relationship between the concentrations of levodopa in plasma and dopamine in the neostriatum. When plasma levodopa was maintained constant by i.v. infusion, the concentration of neostriatal dopamine reached a plateau by 1 h. Increases in dopamine were proportional to the amount of precursor in plasma. The tissue half-life of this dopamine in normal rabbits was not more than 15 min. Half-lives of comparable duration for striatal dopamine were calculated from rabbits treated chronically with levodopa, and from rabbits with monoamine-depleting lesions. The results show that the concentration of dopamine in rabbit neostriatum correlates closely with the concentration of levodopa in plasma. Concurrent analyses of neocortical tissues indicate that the neostriatum may not be different from other brain regions with regard to dopamine storage mechanisms. Interpretation of the results in terms of the clinical use of levodopa suggests that the durations of short-term effects (measured in h) of the drugs are paralleled by changes in concentration of brain dopamine.