Subthalamic infusion of an NMDA antagonist prevents basal ganglia metabolic changes and nigral degeneration in a rodent model of Parkinson's disease.
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 Nmethyl-D-aspartate antagonist MK-801 or the alpha-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.
Blandini
F
F
Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino, Pavia, Italy. blandini@tin.it
Nappi
G
G
Greenamyre
J T
JT
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects*; D020531:Subthalamic Nucleus / Q000187:drug effects*