title: Behavioural impact of a double dopaminergic and serotonergic lesion in the non-human primate.
abstract: Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervating systems is involved in specific basal ganglia territories for different symptoms.
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Beaudoin-Gobert
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Epinat
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Météreau
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Duperrier
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Neumane
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Ballanger
authors.affiliation: 3 CERMEP, Imagerie du vivant, Bron 69677, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Lavenne
authors.affiliation: 3 CERMEP, Imagerie du vivant, Bron 69677, France.
authors.forename: François
authors.initials: F
authors.lastname: Liger
authors.affiliation: 3 CERMEP, Imagerie du vivant, Bron 69677, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Tourvielle
authors.affiliation: 3 CERMEP, Imagerie du vivant, Bron 69677, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bonnefoi
authors.affiliation: 3 CERMEP, Imagerie du vivant, Bron 69677, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Costes
authors.affiliation: 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France 3 CERMEP, Imagerie du vivant, Bron 69677, France 4 Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, UMR 5246 CNRS, Lyon 69622, France 5 Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon 69229, France.
authors.forename: Didier Le
authors.initials: DL
authors.lastname: Bars
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France 5 Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon 69229, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France 5 Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon 69229, France 6 Faculté de médecine, Lyon Sud Charles Mérieux, Université Lyon I, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
authors.forename: Léon
authors.initials: L
authors.lastname: Tremblay
authors.affiliation: 1 Centre de Neuroscience Cognitive, CNRS UMR5229, Bron 69675, France 2 Université Claude Bernard Lyon 1, Villeurbanne 69100, France veronique.sgambato-faure@isc.cnrs.fr veronique.sgambato-faure@inserm.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Sgambato-Faure
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001931:Brain Mapping; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D005260:Female; D007980:Levodopa / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008252:Macaca fascicularis; D008297:Male; D001523:Mental Disorders / Q000209:etiology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009662:Nortropanes; D011877:Radionuclide Imaging; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity; D013440:Sulfides
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D000978:Antiparkinson Agents; D015259:Dopamine Agents; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D018490:Serotonin Agents; D013440:Sulfides; D012701:Serotonin; D007980:Levodopa; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine
keywords: Parkinson’s disease; dyskinesia; monkey; neuropsychiatric symptoms; serotonin