title: Basal ganglia serotonin 1B receptors in parkinsonian monkeys with L-DOPA-induced dyskinesia.
abstract: L-DOPA-induced dyskinesias (LID)s are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease (PD). Serotonin receptors are thought to contribute to LID but serotonin 1B (5-HT1B) receptors have never been investigated in any primate models of PD and LID. Therefore, we measured 5-HT1B receptors with [(3)H]GR 125743 autoradiography in controls, MPTP-lesioned monkeys, and L-DOPA-treated MPTP monkeys, with or without Ro 61-8048 treatment, a kynurenine hydroxylase inhibitor alleviating LID. In normal condition, 5-HT1B receptor specific binding was highest in the substantia nigra pars reticulata (SNr), high in the globus pallidus (GP), nucleus accumbens and substantia innominata and lower in the caudate nucleus and putamen. 5-HT1B receptors were increased in caudate nucleus, putamen and SNr of MPTP monkeys compared to controls. L-DOPA-treated MPTP monkeys had elevated 5-HT1B receptor specific binding in caudate nucleus, putamen, SNr and internal GP. In all these brain regions, increases were prevented by co-administration of Ro 61-8048. No effect of MPTP lesion or treatment was observed for 5-HT1B specific binding in the external GP, nucleus accumbens and substantia innominata. This study is the first description in primates of altered brain 5-HT1B receptors associated with prevention of LID.
authors: Faculty of Pharmacy, Université Laval, Quebec City, Canada, G1K 7P4; Neuroscience Research Unit, Centre de recherche du CHU de Québec, Quebec City, Canada, G1V 4G2; Centre de Recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Canada, G1J 2G3.
authors: Golnasim
authors: G
authors: Riahi
authors: Marc
authors: M
authors: Morissette
authors: Pershia
authors: P
authors: Samadi
authors: Martin
authors: M
authors: Parent
authors: Thérèse
authors: T
authors: Di Paolo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000517:prevention & control; D007980:Levodopa / Q000009:adverse effects*; D008252:Macaca fascicularis; D010300:Parkinson Disease / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D001549:Benzamides; C107225:N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl)-3-methyl-4-(4-pyridyl)benzamide; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; C110196:Ro 61-8048; D013449:Sulfonamides; D013844:Thiazoles; D012701:Serotonin; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: 5-HIAA; 5-HT; 5-hydroxyindoleacetic acid; 5-hydroxytryptamine (serotonin); 6-OHDA; 6-hydroxydopamine; Basal ganglia; GABA; GAD; L-DOPA; LID; MPTP; Neurodegenerative disorders; PD; Parkinson's disease; Primate; Serotonin receptor 1B; ac; anterior commissure; gamma-aminobutyric acid; glutamic acid decarboxylase; l-3,4-dihydroxyphenylalanine; l-DOPA-induced dyskinesia