DOPAMINE METABOLISM IN THE GUINEA-PIG STRIATUM - ROLE OF MONOAMINE OXIDASE-A AND OXIDASE-B

These studies were carried out to determine whether the greater abunda nce of monoamine oxidase B in the guinea pig affects the actions of (- )-deprenyl on dopamine metabolism in whole tissue or in extracellular fluid. The administration of (-)-deprenyl in doses that do not affect monoamine oxidase A activity (1 -4 mg kg - 1, 2 h) increases striatal 2-phenylethylamine and dopamine concentrations and reduces 3,4-dihydro xyphenylacetic acid. No effects were observed on striatal homovanillic acid, 5-HT and 5-hydroxyindole acetic acid. Inhibition of monoamine o xidase A with clorgyline with doses up to 8 mg kg-1 (2 h) does not aff ect striatal 2-phenylethylamine but increases dopamine and 5-HT concen trations and reduces 3,4-dihydroxyphenylacetic acid and 5-hydroxyindol e acetic acid. (-)-Deprenyl (2-4 mg kg-1) did not change the extracell ular concentrations of dopamine but the higher dose produced a limited reduction in extracellular 3,4-dihydroxyphenylacetic acid. Inhibition of monoamine oxidase A and monoamine oxidase B with pargyline (75 mg kg-1, 2 h) significantly increased the levels of extracellular dopamin e and reduced those of their acid metabolites. These results show that in the guinea pig striatum inhibition of monoamine oxidase B by (-)-d eprenyl impairs the metabolism of dopamine in the whole tissue but doe s not produce a marked increase in extracellular dopamine.