Premium
Subthalamic infusion of an NMDA antagonist prevents basal ganglia metabolic changes and nigral degeneration in a rodent model of Parkinson's disease
Author(s) -
Blandini Fabio,
Nappi Giuseppe,
Greenamyre J. Timothy
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.104
Subject(s) - nbqx , basal ganglia , subthalamic nucleus , antagonist , glutamate receptor , neuroprotection , nmda receptor , medicine , lesion , parkinson's disease , neuroscience , pharmacology , anesthesia , biology , central nervous system , pathology , ampa receptor , disease , deep brain stimulation , receptor
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. Ann Neurol 2001;49:525–529