title: Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys.
abstract: Subthalamotomy allows a reduction of doses of l-DOPA in dyskinetic patients while its antiparkinsonian benefits are preserved. However, the mechanisms of the potentiation of this response to medication remain to be elucidated. Hence, dopamine D1 and D2 receptors as well as the dopamine transporter were investigated using receptor binding autoradiography. D1 and D2 receptors as well as preproenkephalin and preprodynorphin mRNA levels were measured by in situ hybridization. Four dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys that underwent unilateral subthalamotomy were compared to four controls, four saline-treated and four l-DOPA-treated MPTP monkeys. Dopamine, its metabolites and its transporter were extensively and similarly decreased in all parkinsonian monkeys. D1 receptor specific binding was decreased in the striatum of all MPTP monkeys. The l-DOPA-induced decrease in D1 receptor specific binding was reversed in the striatum ipsilateral to subthalamotomy. D1 receptor mRNA levels followed a similar pattern. D2 receptor specific binding and mRNA levels remained unchanged in all groups. Striatal preproenkephalin mRNA levels were overall increased in MPTP monkeys; the STN-lesioned parkinsonian group had significantly lower values than the saline-treated and l-DOPA-treated parkinsonian monkeys in the dorsolateral putamen. Striatal preprodynorphin mRNA levels remained unchanged in MPTP monkeys compared to controls whereas it increased in all monkeys treated with l-DOPA compared to controls; subthalamotomy induced a decrease in the dorsolateral putamen ipsilateral to surgery. The improved motor response to l-DOPA after subthalamotomy in the parkinsonian monkeys investigated may be associated with an increased synthesis and expression of D1 receptors ipsilateral to STN lesion of the direct pathway.
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada; Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Jourdain
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada; Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Morin
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Grégoire
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada; Faculty of Pharmacy, Laval University, Quebec, QC, Canada. Electronic address: therese.dipaolo@crchul.ulaval.ca.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D007980:Levodopa / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy / Q000601:surgery*; D008252:Macaca fascicularis; D010052:Ovariectomy; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000502:physiology*; D020530:Subthalamus / Q000502:physiology* / Q000601:surgery*
chemical_list: D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D007980:Levodopa
keywords: Dopamine receptors; Dyskinesia; MPTP monkey; Parkinson's disease; Subthalamotomy