TOWARD AN UNDERSTANDING OF THE ROLE OF GLUTAMATE IN EXPERIMENTAL PARKINSONISM - AGONIST-SENSITIVE SITES IN THE BASAL GANGLIA

Citation
T. Klockgether et L. Turski, TOWARD AN UNDERSTANDING OF THE ROLE OF GLUTAMATE IN EXPERIMENTAL PARKINSONISM - AGONIST-SENSITIVE SITES IN THE BASAL GANGLIA, Annals of neurology, 34(4), 1993, pp. 585-593
Citations number
36
Categorie Soggetti
Clinical Neurology",Neurosciences
Journal title
ISSN journal
03645134
Volume
34
Issue
4
Year of publication
1993
Pages
585 - 593
Database
ISI
SICI code
0364-5134(1993)34:4<585:TAUOTR>2.0.ZU;2-B
Abstract
Increased glutamatergic transmission in the basal ganglia is implicate d in the pathophysiology of Parkinson's disease. However, the mechanis ms by which activation of glutamate receptors produce parkinsonism are unknown. Therefore, we examined whether the glutamate agonists N-meth yl-D-aspartate (NMDA), pha-amino-3-hydroxy-5-methyl-4-isoxazolepropion ate (AMPA), kainate, and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxy late produce parkinsonism in rats after microapplication into differen t subregions of the basal ganglia. Electromyographic activity was used as a measure of parkinsonian rigidity. We found that in the rostral s triatum, excitation mediated by NMDA but not by non-NMDA receptors led to parkinsonism. In the substantia nigra pars reticulata, internal pa llidal segment/entopeduncular nucleus, and subthalamic nucleus, activa tion of AMPA/kainate and metabotropic receptors but not of NMDA recept ors led to parkinsonian rigidity. Rigidity occurred also in animals be aring ibotenate-induced lesions of the posterior part of the striatum and of the external pallidal segment, but not in animals with lesions of the anterior striatum, subthalamic nucleus, internal pallidal segme nt/entopeduncular nucleus, or substantia nigra pars reticulata. These observations suggest that the activation of glutamate receptor subtype s in the basal ganglia may be differentially involved in the expressio n of parkinsonian symptoms.