title: Striatal AMPA receptor binding is unaltered in the MPTP-lesioned macaque model of Parkinson's disease and dyskinesia.
abstract: Long-term levodopa or dopamine agonist treatment in the MPTP-lesioned primate model of Parkinson's disease elicits dyskinesia, which is phenotypically similar to levodopa-induced dyskinesia in patients with Parkinson's disease. AMPA receptor antagonists have previously been shown to have both anti-parkinsonian and anti-dyskinetic actions in MPTP-lesioned primates, suggesting that AMPA receptor transmission is functionally overactive under these conditions. In this study, we investigated the level of striatal AMPA receptor binding in the MPTP lesioned primate using the selective AMPA ligand (3)H-(S)-5-fluorowillardiine. AMPA receptor binding was studied in non-parkinsonian, non-dyskinetic parkinsonian, and dyskinetic macaques. Striatal AMPA receptor binding was not different in any of the treatment groups (P > 0.05). Although AMPA receptor-mediated transmission is functionally overactive in Parkinson's disease and dyskinesia, changes in striatal AMPA receptor levels are not likely to be the cause of such movement disorders.
authors.affiliation: Manchester Movement Disorders Laboratory, Manchester, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Silverdale
authors.forename: A R
authors.initials: AR
authors.lastname: Crossman
authors.forename: J M
authors.initials: JM
authors.lastname: Brotchie
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000009:adverse effects / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D009928:Organ Specificity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology; D011869:Radioligand Assay; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D011743:Pyrimidines; D018091:Receptors, AMPA; C095178:5-fluorowillardiine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine; D000409:Alanine