title: Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications.
abstract: L-DOPA-induced dyskinesias (LID) are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease. Serotonin receptors are implicated in the development of LID and modulation of basal ganglia 5-HT1B receptors is a potential therapeutic alternative in Parkinson's disease. In the present study, we used receptor-binding autoradiography of the 5-HT1B-selective radioligand [3H]GR125743 to investigate possible contributions of changes in ligand binding of this receptor in LID in post-mortem brain specimens from Parkinson's disease patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist and has been shown to reduce the development of LID in these monkeys in a chronic treatment of one month. [3H]GR125743 specific binding to striatal and pallidal 5-HT1B receptors respectively were only increased in L-DOPA-treated MPTP monkeys (dyskinetic monkeys) as compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesias scores correlated positively with this binding. Parkinson's disease patients with motor complications (L-DOPA-induced dyskinesias and wearing-off) had higher [3H]GR125743 specific binding compared to those without motor complications and controls in the basal ganglia. Reduction of motor complications was associated with normal striatal 5-HT1B receptors, suggesting the potential of this receptor for the management of motor complications in Parkinson's disease.
authors.affiliation: Faculty of Pharmacy, Université Laval, Quebec City, G1K 7P4, Canada; Neuroscience Research Unit, Centre de recherche du CHU de Québec, Quebec City, G1V 4G2, Canada. Electronic address: nicolas.morin.4@ulaval.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Morin
authors.affiliation: Neuroscience Research Unit, Centre de recherche du CHU de Québec, Quebec City, G1V 4G2, Canada. Electronic address: marc.morissette@crchudequebec.ulaval.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.affiliation: Neuroscience Research Unit, Centre de recherche du CHU de Québec, Quebec City, G1V 4G2, Canada. Electronic address: laurent.gregoire@crchudequebec.ulaval.ca.
authors.forename: Laurent
authors.initials: L
authors.lastname: Grégoire
authors.affiliation: Division of Neurology, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, S7N 0W8, Canada. Electronic address: ahr128@campus.usask.ca.
authors.forename: Alex
authors.initials: A
authors.lastname: Rajput
authors.affiliation: Division of Neurology, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, S7N 0W8, Canada. Electronic address: Ali.Rajput@saskatoonhealthregion.ca.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.affiliation: Faculty of Pharmacy, Université Laval, Quebec City, G1K 7P4, Canada; Neuroscience Research Unit, Centre de recherche du CHU de Québec, Quebec City, G1V 4G2, Canada. Electronic address: therese.dipaolo@crchul.ulaval.ca.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000633:toxicity*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D010052:Ovariectomy; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D044302:Receptor, Serotonin, 5-HT1B; D007980:Levodopa; C121465:6-methyl-2-(phenylethynyl)pyridine
keywords: 5-HT(1B) serotonin receptor; Human; MPTP-lesioned monkey; Parkinson's disease; l-DOPA-induced dyskinesia