Blockade of subthalamic glutamatergic activity corrects changes in neuronal metabolism and motor behavior in rats with nigrostriatal lesions.
We infused--for four weeks--a selective antagonist of the NMDA receptor, MK-801, into the subthalamic nucleus of rats bearing an evolving nigrostriatal lesion. The aim was to block the subthalamic overactivity resulting from the dopaminergic striatal denervation. The nigrostriatal lesion caused metabolic activation--increased activity of the mitochondrial enzyme succinate dehydrogenase--of basal ganglia nuclei, ipsilaterally to the lesion, along with contralateral rotational behavior. These phenomena were effectively counteracted by the blockade of glutamatergic transmission at the subthalamic level. Pharmacological manipulation of the STN, through selective drugs capable of modulating glutamatergic transmission, may therefore represent a valuable tool for the treatment of PD.
Blandini
F
F
C Mondino Neurological Institute, Pavia, Italy.
Greenamyre
J T
JT
Fancellu
R
R
Nappi
G
G
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013565:Sympatholytics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D013565:Sympatholytics; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D000661:Amphetamine; D013385:Succinate Dehydrogenase