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Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evaluate the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy,(More)
The pathogenesis of the motor fluctuations that complicate levodopa treatment of most parkinsonian patients remains uncertain. To evaluate the contribution of the degree of dopamine neuron loss and the duration of levodopa exposure, rats whose nigrostriatal system had been previously lesioned unilaterally by 6-hydroxydopamine received twice daily levodopa(More)
Dopamine influence in the striatum is essential to motor behavior and may lead to involuntary movements in pathologic conditions. The basic mechanisms lie in differential dopamine responses of medium spiny neurons (MSNs) contributing to striatal output pathways. The relationship between striatal discharge and mobility is thus critical to understanding the(More)
The complex dopamine-glutamate interactions within the basal ganglia are disrupted by chronic nigrostriatal denervation and standard replacement therapy with levodopa. Acute N-methyl-D-aspartate (NMDA) receptor blockade is able to overcome the changes in dopamine D1- and D2-dependent responses and the progressive shortening in the duration of response(More)
Excitatory amino acid antagonists have been proposed as novel therapeutic agents for Parkinson's disease due to their ability to reverse akinesia in animal models of this disorder. To further evaluate this therapeutic potential, we examined the effects of a N-methyl-D-aspartate (NMDA) and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)(More)
Dopaminoceptive system alterations in the basal ganglia have been implicated in the pathogenesis of wearing-off fluctuations that complicate levodopa therapy of Parkinson's disease. To evaluate the contribution of glutamatergic mechanisms to the associated changes in striatal efferent pathway function, we examined the ability of N-methyl-D-aspartate (NMDA)(More)
The effect of dizocilpine (MK-801) on dopaminergic agonist-induced rotational behavior was investigated in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway after chronic administration of levodopa. The rotational response to the D2 agonist quinpirole was markedly increased in levodopa-treated animals compared with rats chronically(More)
The cortical electromyogram (EMG) activity, preceding voluntary movements, was recorded in 12 normal subjects in two different situations: first, when movements were self-induced by the subjects by their own will; and second, in response to threshold electrical stimulation of the index finger, a brief flash of a light-emitting diode (LED), and a click. Four(More)
The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi of parkinsonian monkeys continuously(More)
Long-term dopamine replacement therapy in Parkinson's disease leads to the development of disabling involuntary movements named dyskinesias that are related to adaptive changes in striatal signaling pathways. The chronic transcription factor DeltaFosB, which is overexpressed in striatal neurons after chronic dopaminergic drug exposure, is suspected to(More)