mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys.
Modulation of excessive glutamatergic transmission within the basal ganglia is considered as an alternative approach to reduce l-Dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). In this study receptor binding autoradiography of [3H]MPEP, a metabotropic glutamate receptor 5 (mGluR5) selective radioligand, was used to investigate possible changes in mGluR5 in the basal ganglia of l-Dopa-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys having developed LIDs compared to animals in which LIDs was prevented by adjunct treatments. LIDs were associated with an increase of mGluR5 specific binding in the posterior putamen and pallidum (+41% and +56%) compared to controls. By contrast, prevention of dyskinesias was associated with an important decrease of mGluR5 specific binding in these areas (-37% and -48%) compared with dyskinetic animals. Moreover, an upregulation (+34%) of mGluR5 receptor binding was seen in the anterior caudate nucleus of saline treated MPTP monkeys. This study is the first to provide evidence that enhanced mGluR5 specific binding in the posterior putamen and pallidum may contribute to the pathogenesis of LIDs in PD.
Samadi
Pershia
P
Molecular Endocrinology and Oncology Research Centre, Laval University Medical Centre, Quebec, Canada; Faculty of Pharmacy, Laval University, Quebec, Canada.
Grégoire
Laurent
L
Morissette
Marc
M
Calon
Fréderic
F
Hadj Tahar
Abdallah
A
Dridi
Mehdi
M
Belanger
Nancy
N
Meltzer
Leonard T
LT
Bédard
Paul J
PJ
Di Paolo
Thérèse
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008252:Macaca fascicularis; D010052:Ovariectomy; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014018:Tissue Distribution
D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine