MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats

The systemic administration of the N-methyl- d-aspartate (NMDA) receptor antagonist, MK801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), has previously been found to reverse the motor response alterations that develop during long-term levodopa treatment of parkinsonian rats. To...

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Bibliographic Details
Published in:Brain research 1996-10, Vol.736 (1), p.202-205
Main Authors: Marin, Concepció, Papa, Stella, Engber, Thomas M., Bonastre, Mercb, Tolosa, Eduardo, Chase, T.N.
Format: Article
Language:English
Subjects:
6-Hydroxydopamine
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
Antiparkinson Agents - antagonists & inhibitors
Antiparkinson Agents - pharmacology
Benserazide - pharmacology
Biological and medical sciences
Dizocilpine Maleate - pharmacology
Levodopa
Levodopa - analogs & derivatives
Levodopa - antagonists & inhibitors
Levodopa - pharmacology
Male
Medical sciences
MK801
Motor Activity - drug effects
Motor fluctuation
Neuropharmacology
Oxidopamine
Parkinson Disease - physiopathology
Pharmacology. Drug treatments
Prosencephalon
Rats
Rats, Sprague-Dawley
Rotation
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Summary:The systemic administration of the N-methyl- d-aspartate (NMDA) receptor antagonist, MK801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), has previously been found to reverse the motor response alterations that develop during long-term levodopa treatment of parkinsonian rats. To determine whether co-administration of MK801 with levodopa might prevent the initial appearance of these response changes, rats, rendered parkinsonian by a 6-hydroxydopamine lesion of the medial forebrain bundle, received either levodopa alone or levodopa with the NMDA receptor antagonist. After four weeks of treatment with levodopa alone, the duration of the turning response declined by 37% ( P < 0.05) and the number of ineffectual levodopa injections had more than doubled ( P < 0.05). MK801 co-treatment completely blocked the shortening in response duration and prevented the frequency of ineffectual levodopa injection from exceeding baseline levels in animals receiving levodopa alone. The total magnitude of the turning response to levodopa was not affected. These results suggest that NMDA receptor blockade may act prophylactically to prevent the appearance of motor response alterations in levodopa-treated parkinsonian rodents that resemble those occurring in levodopa-treated patients with Parkinson's disease.
ISSN:0006-8993
1872-6240
DOI:10.1016/0006-8993(96)00693-2