Dopamine release in rat striatum after administration of l-DOPA as studied with in vivo electrochemistry

The time-course of changes in dopamine (DA) release induced by systemic administration of l-DOPA was studied in the rat striatum using electrochemistry in vivo. Recordings were obtained from anesthetized animals in which carbon paste microelectrodes were implanted stereotaxically into the striatum. Chronoamperometric measurements were made by applying 0.8 V for 1 sec, with an interval of 5 min between measurements; in some experiments, the potential was scanned every 5 min from 0 to 1.0 V. Administration of l-DOPA (50 mg/kg) after pretreatment with an inhibitor of peripheral aromatic amino acid decarboxylase (AAAD) produced a large rise in chronoamperometric currents, lasting for about 6 h. Different approaches were used to determine whether DOPA, DA or DA metabolites (all of which are oxidized at the potential chosen) were responsible for these DOPA-induced increases. (1) Rats were killed at different times after l-DOPA administration, and their striata were analyzed biochemically for DOPA, DA, and DA metabolites. Comparison of time-courses indicated that the rise in chronoamperometric responses correlated with elevations in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels rather than with those of DOPA or DA, suggesting that DA metabolites contribute significantly to the increases in chronoamperometric responses observed after administration of l-DOPA. (2) Administration of l-DOPA after pretreatment with an inhibitor of central AAAD, a treatment that results in large increases in striatal DOPA levels but abolishes l-DOPA-induced formation of DA and DA metabolites (measured biochemically), failed to increase chronoamperometric responses. This finding indicates that exogenous l-DOPA entering the striatum is not detected with this technique and that it must be decarboxylated to produce the elevations of currents. (3) In animals pretreated with an inhibitor of monoamine oxidase to abolish formation of DOPAC and HVA, l-DOPA administration produced only a small and short lasting increase in chronoamperometric responses, despite sustained and large increases in striatal DA concentrations. By using the potential-scanning technique we showed that these increases in electrochemical responses occur at a potential at which DA but not methylated catechols are oxidized. These findings indicate that DA contributes only a small fraction (limited to the initial rise) of the large increases in chronoamperometric responses recorded in the striatum after administration of l-DOPA. This suggests that administration of l-DOPA may produce only a short-lasting increase in striatal DA release, despite a more prolonged rise in striatal DA concentration.