L-3,4-DIHYDROXYPHENYLALANINE-INDUCED DOPAMINE RELEASE IN THE STRIATUMOF INTACT AND 6-HYDROXYDOPAMINE-TREATED RATS - DIFFERENTIAL-EFFECTS OF MONOAMINE OXIDASE-A AND OXIDASE-B INHIBITORS

Administration of L-DOPA (50 mg/kg) elicits a significant increase in extracellular dopamine in striata of rats treated with the catecholami nergic neurotoxin 6-hydroxydopamine but not in striata of intact rats. To assess the role of dopaminergic nerve terminals in determining the effects of exogenous L-DOPA on extracellular dopamine levels in stria tum, we examined the relative contributions of monoamine oxidase A and monoamine oxidase B to the catabolism of dopamine synthesized from ex ogenous L-DOPA. Extracellular concentrations of dopamine and its catab olite, 3,4-dihydroxyphenylacetic acid, were monitored with in vivo dia lysis in striata of intact rats and of rats with unilateral 6-hydroxyd opamine lesions of striatal dopamine. Clorgyline (2 mg/kg), an inhibit or of monoamine oxidase A, significantly increased dopamine and decrea sed 3,4-dihydroxyphenylacetic acid in intact but not in dopamine-deple ted striata. Inhibition of monoamine oxidase B with either L-deprenyl (1 mg/kg) or Ro 19-6327 (1 mg/kg) did not significantly affect dopamin e or 3,4-dihydroxyphenylacetic acid in striata of intact or dopamine-d epleted rats. In intact rats, administration of clorgyline in conjunct ion with L-DOPA produced a >20-fold increase in dopamine and prevented the L-DOPA-induced increase in 3,4-dihydroxyphenylacetic acid. Althou gh both L-deprenyl and Ro 19-6327 administered in combination with L-D OPA elicited a small but significant increase in dopamine, levels of 3 ,4-dihydroxyphenylacetic acid were not affected. In rats pretreated wi th 6-hydroxydopamine, clorgyline had no significant effect on the incr eases in dopamine and 3,4-dihydroxyphenylacetic acid elicited by L-DOP A. Furthermore, neither L-deprenyl nor Ro 19-6327 affected L-DOPA-indu ced increases in dopamine and 3,4-dihydroxyphenylacetic acid in dopami ne-depleted striata. The present findings indicate that deamination by monoamine oxidase A is the primary mechanism for catabolism of striat al dopamine, both under basal conditions and after administration of e xogenous L-DOPA. Loss of dopaminergic terminals eliminates this action of monoamine oxidase A but does not enhance deamination by monoamine oxidase B. These data support a model in which exogenous L-DOPA elicit s enhanced extracellular accumulation of dopamine in the dopamine-depl eted striatum because some transmitter synthesis occurs at nondopamine rgic sites and the dopamine terminals that normally take up and catabo lize this pool of transmitter are absent.