L-DOPA METABOLISM IN CORTICAL AND STRIATAL TISSUES IN AN ANIMAL-MODEL OF PARKINSONISM

Rats with unilateral 6-hydroxydopamine lesions of the midbrain tegmentum were treated with 25 mg/kg L-DOPA methyl ester/2 mg/kg carbidopa. The effects of the L-DOPA treatment upon serum, neocortical, and striatal L-DOPA and 3-O-methyl dopa (3-OMD) concentrations were measured. The highest L-DOPA and 3-OMD concentrations were obtained in the serum and in a ratio of approximately 2:1. In the brain, there was a uniform distribution of 3-OMD but L-DOPA concentrations were highly nonhomogeneous. Regression line equations for the statistically significant correlation coefficients between L-DOPA and tissue dopamine concentrations suggested that L-DOPA generated 50-60 times as much dopamine in the intact striatum as in cortex. The regional variation of L-DOPA concentration appears related to the capability of the brain tissue to generate and store dopamine from L-DOPA, In addition, the findings suggest that the behavioral ineffectiveness of L-DOPA in intact animals is related to its capacity to transform L-DOPA to tissue bound dopamine.