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
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.