title: mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys.
abstract: 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.
authors.affiliation: Molecular Endocrinology and Oncology Research Centre, Laval University Medical Centre, Quebec, Canada; Faculty of Pharmacy, Laval University, Quebec, Canada.
authors.forename: Pershia
authors.initials: P
authors.lastname: Samadi
authors.forename: Laurent
authors.initials: L
authors.lastname: Grégoire
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.forename: Fréderic
authors.initials: F
authors.lastname: Calon
authors.forename: Abdallah
authors.initials: A
authors.lastname: Hadj Tahar
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dridi
authors.forename: Nancy
authors.initials: N
authors.lastname: Belanger
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Meltzer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bédard
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: 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
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine