Long term L-DOPA treatment causes production of 6-OHDA in the mouse striatum: Involvement of hydroxyl radical

Abstract

Background: L-DOPA (3,4-dihydroxyphenylalanine), the precursor of dopamine (DA) still remains the mainstay drug for the treatment of Parkinson's disease (PD). L-DOPA is not well regulated at the dopaminergic neurons due to excessive DA production from the anti-parkinsonian drug, it has been generally believed that several cytotoxic molecules could be generated in the brain following activation by dopaminomimetics and DA catabolism inhibitors. Purpose: The present study examines the production of 6-OHDA in the striatum of mice treated sub-acutely with L-DOPA, and investigates the possible mechanism of 6-OHDA production from DA. Methods: Male adult Balb/c mice were treated with different doses of L-DOPA/carbidopa combination (25, 250 and 500 / 2.5, 25 and 50 mg/kg, p.o) or vehicle for 7 days and 6-OHDA levels were analyzed in the striatum at 1, 2, 4 and 6 h after the last dose of the drug. Results: We report here that prolonged L-DOPA treatment in mice causes significant elevation in 6-OHDA production from 1–6 h after the drug treatment, which is dependent on the dose of L-DOPA administered. Dopamine utilization was evident from the reduced levels of its presence in the FAD system following 6-OHDA production. Conclusion: These results point to an inherent hazard of long-term administration of L-DOPA in Parkinson's disease patients. doi : 10.5214/ans.0972.7531.2009.160406 Competing interests: None. Source of Funding: CSIR Received Date: 02 Sept 2009 Revised Date: 04 Oct 2009 Accepted Date: 14 Oct 2009