Toward an understanding of the role of glutamate in experimental parkinsonism: agonist-sensitive sites in the basal ganglia.
Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease. However, the mechanisms by which activation of glutamate receptors produce parkinsonism are unknown. Therefore, we examined whether the glutamate agonists N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate produce parkinsonism in rats after microapplication into different subregions of the basal ganglia. Electromyographic activity was used as a measure of parkinsonian rigidity. We found that in the rostral striatum, excitation mediated by NMDA but not by non-NMDA receptors led to parkinsonism. In the substantia nigra pars reticulata, internal pallidal segment/entopeduncular nucleus, and subthalamic nucleus, activation of AMPA/kainate and metabotropic receptors but not of NMDA receptors led to parkinsonian rigidity. Rigidity occurred also in animals bearing 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 segment/entopeduncular nucleus, or substantia nigra pars reticulata. These observations suggest that the activation of glutamate receptor subtypes in the basal ganglia may be differentially involved in the expression of parkinsonian symptoms.
Klockgether
T
T
Department of Neurology, University of Tübingen, Berlin, Germany.
Turski
L
L
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004576:Electromyography; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000503:physiopathology; D016202:N-Methylaspartate / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D005971:Glutamates; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid