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NMDA receptor blockade reverses motor response alterations induced by levodopa
T M Engber1, S M Papa, R C Boldry
1Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
Neuroreport
|December 20, 1994
Summary
Motor fluctuations in Parkinson's disease patients treated with levodopa may involve neuronal plasticity. Blocking N-methyl-D-aspartate (NMDA) receptors reversed these levodopa-induced motor response changes in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Neurology
Background:
- Levodopa therapy is crucial for Parkinson's disease (PD) but often leads to motor fluctuations.
- These fluctuations may stem from behavioral or neuronal plasticity.
- Glutamate transmission via N-methyl-D-aspartate (NMDA) receptors is implicated in various forms of neuronal plasticity.
Purpose of the Study:
- To investigate the role of NMDA receptor-mediated mechanisms in the development of motor response alterations to chronic levodopa therapy.
- To evaluate the effect of NMDA receptor blockade on these levodopa-induced changes in a rat model of Parkinson's disease.
Main Methods:
- Hemiparkinsonian rats were administered levodopa repeatedly.
- The study assessed changes in rotational behavior induced by D1 and D2 dopamine receptor agonists.
- The duration of the motor response to levodopa was also measured.
- Acute pretreatment with the NMDA antagonist MK-801 was performed.
Main Results:
- Repeated levodopa administration altered motor responses, including decreased D1 agonist-induced rotation and increased D2 agonist-induced rotation.
- The duration of the motor response to levodopa progressively reduced with chronic treatment.
- Acute NMDA receptor blockade with MK-801 completely reversed all observed levodopa-induced motor alterations.
Conclusions:
- NMDA receptor-mediated mechanisms contribute significantly to the behavioral plasticity observed with chronic levodopa treatment in Parkinson's disease models.
- NMDA receptor antagonists show potential for reversing motor response complications associated with long-term levodopa therapy in Parkinson's disease.