title: Normalization of GABAA receptor specific binding in the substantia nigra reticulata and the prevention of L-dopa-induced dyskinesias in MPTP parkinsonian monkeys.
abstract: L-Dopa therapy in Parkinson's disease (PD) is counfounded by the development of involuntary movements such as L-Dopa-induced dyskinesias (LIDs). In this study GABA(A) receptor autoradiography was assessed using [(3)H]flunitrazepam binding to the benzodiazepine site of the GABA(A) receptor and [(35)S]t-butylbicyclophosphorothionate (TBPS) binding to the chloride channel of GABA(A) receptors in the substantia nigra reticulata (SNr) and subthalamic nucleus (STN). L-Dopa-treated parkinsonian monkeys experiencing LIDs were compared to animals in which LIDs was prevented by adjunct treatments with CI-1041, a selective antagonist of the NR1A/2B subtype of NMDA receptor, or low doses of the dopamine D2 receptor agonist, cabergoline. Our results demonstrated a decrease of GABA(A) receptor specific binding in the posterior part of the SNr in dyskinetic monkeys compared to nondyskinetic animals, while no modulation has been observed in the STN. These results provide evidence for the first time that pharmacological treatments preventing LIDs in nonhuman primate model of PD are associated with normalization of GABA(A) receptor-mediated signalling in the SNr.
authors.affiliation: Molecular Endocrinology and Oncology Research Centre, Laval University Medical Centre, Quebec, Canada.
authors.forename: Pershia
authors.initials: P
authors.lastname: Samadi
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: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D001583:Benzoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003292:Convulsants / Q000378:metabolism; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D007554:Isotopes / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects*; D008252:Macaca fascicularis; D010052:Ovariectomy / Q000379:methods; D020734:Parkinsonian Disorders / Q000188:drug therapy; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D011859:Radiography; D018079:Receptors, GABA / Q000378:metabolism*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology
chemical_list: D000978:Antiparkinson Agents; D001583:Benzoxazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D018757:GABA Modulators; D007554:Isotopes; D010880:Piperidines; D018079:Receptors, GABA; D007980:Levodopa; C481484:besonprodil; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate