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Chronic L-dopa administration decreases striatal accumulation of dopamine from exogenous L-dopa in rats with intact nigrostriatal projections

Laboratory of Clinical Neurochemistry, Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.

To examine whether chronic administration of L-dopa can affect its own utilization in striatum, rats were injected once daily for 30 days with l-dopa and carbidopa or with saline. On day 31, saline and l-dopa animals were sacrificed 1, 2, or 3 hours after l-dopa injection. In rats given long-term l-dopa, the elevations in striatal dopamine concentrations induced by l-dopa administration were smaller and of shorter duration than those in controls. Such changes did not occur in animals pretreated with l-dopa for only 10 days. Results suggest that prolonged l-dopa therapy may decrease striatal accumulation of dopamine from exogenous l-dopa even when the nigrostriatal projections are intact. Therefore, it is possible that declining efficacy of l-dopa in parkinsonism may be due to effects of the drug itself and not only to disease progression.

Address correspondence and reprint requests to Dr. Melamed, Department of Neurology, Hadassah University Hospital, Jerusalem. P.O.B. 12000, Israel.

Supported in part by the U.S.A.-Israel Binational Science Foundation Grant No. 2348, by the Chief Scientist's Office, Ministry of Health, Israel, and by a grant from the Warschaw family in honor of L. A. Harvey.

Presented in part at the thirty-fourth annual meeting of the American Academy of Neurology, Washington, DC, April 1982

Accepted for publication November 8, 1982.

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