MODULATION OF TYROSINE-HYDROXYLASE AND AROMATIC L-AMINO-ACID DECARBOXYLASE AFTER INHIBITING MONOAMINE OXIDASE-A

After acute administration of the monoamine oxidase inhibitor clorgyli ne there is a reduction of aromatic L-amino acid decarboxylase and tyr osine hydroxylase activity in the mouse striatum. Similar responses we re seen after administering the non-selective monoamine oxidase inhibi tor pargyline and high, but not low, doses of the selective monoamine oxidase-B inhibitor deprenyl. Changes of tyrosine hydroxylase activity were observed only when subsaturated concentrations of the pteridine cofactor were used for the assay. The monoamine oxidase inhibitors alt ered the abundance of aromatic L-amino acid decarboxylase and tyrosine hydroxylase mRNA in the midbrain. Pargyline and high doses of depreny l increased aromatic L-amino acid decarboxylase mRNA, while clorgyline initially decreased and then increased it. All three compounds caused an early decrease of tyrosine hydroxylase mRNA. The acidic metabolite s of dopamine appeared most affected by pargyline and clorgyline, supp orting the notion that deamination of striatal dopamine in rodents is primarily by monoamine oxidase-A. Our results suggest that striatal ty rosine hydroxylase and aromatic L-amino acid decarboxylase are apparen tly modulated via different mechanisms in response to perturbation of dopamine metabolism.