Using permanent cannulas connected to subcutaneous pumps, we infused selective glutamate antagonists into the subthalamic nucleus of rats. Pumps were implanted immediately after the intrastriatal injection of 6-hydroxydopamine and delivered micro-quantities of the N-methyl-D-aspartate antagonist MK-801 or the α-amino-3-hydroxy-5-methylisoxazole antagonist NBQX for 4 weeks. Subthalamic infusion of MK-801, but not of NBQX, prevented the basal ganglia metabolic changes and motor abnormalities caused by nigrostriatal lesion. Animals treated with MK-801 also exhibited marked reduction of nigral cell loss. We conclude that pharmacological modulation of subthalamic activity may have both symptomatic and neuroprotective effects in Parkinson's disease.
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