title: Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.
abstract: Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Farré
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Reyes-Resina
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.
authors.forename: Júlia
authors.initials: J
authors.lastname: Canet-Pons
authors.affiliation: Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Iria G
authors.initials: IG
authors.lastname: Dopeso-Reyes
authors.affiliation: Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Rico
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Lluís
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortés
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Labandeira-García
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.affiliation: Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Diagonal 645, Prevosti Building, 08028, Barcelona, Spain. rfranco@ub.edu.|Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. rfranco@ub.edu.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. rfranco@ub.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D019281:Dimerization; D004292:Dominance, Cerebral / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology* / Q000633:toxicity; D008252:Macaca fascicularis; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D004298:Dopamine
keywords: Basal ganglia; Caudate; D3 receptors; Direct pathway; Dopamine receptor heteromers; Dopamine sensitivity; Indirect pathway; L-DOPA; Lateralization; Macaca fascicularis; Non-human primate; Parkinson’s; Putamen; Striatum