Long‐term administration of L‐DOPA does not damage dopaminergic neurons in the mouse

To examine the possibility that long-term L-DOPA therapy may be toxic to and destroy nigrostriatal dopaminergic neurons, mice were given large doses of L-DOPA (200 mg per animal per day) for 18 months. L-DOPA treatment was then discontinued to allow washout of drug from brain; 8 days later, L-DOPA was undetectable in corpora striata. Biochemical indices of the integrity of nigrostriatal neurons (striatal dopamine and DOPAC concentrations and activities of tyrosine hydroxylase and DOPA decarboxylase) were equal in DOPA-treated and control mice, suggesting that prolonged L-DOPA administration did not damage nigrostriatal neurons.