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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)
Drugs acting at cannabinoid type 1 receptors (CB1) have modulatory effects on glutamate and GABA neurotransmission in basal ganglia; thus, they potentially affect motor behavior in the parkinsonian setting. Preclinical trials with diverse cannabinoid agents have shown varied results, and the precise effects of blocking cannabinoid CB1 receptors remain(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)
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 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)
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)
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)
The non-human primate MPTP model of Parkinson's disease is an essential tool for translational studies. However, the currently used methodologies to produce parkinsonian monkeys do not follow unified criteria, and the applied models may often fall short of reproducing the characteristics of patients in clinical trials. Pooling of data from the parkinsonian(More)
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(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)