title: Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson's disease.
abstract: Serotonin transporter blockade with selective serotonin reuptake inhibitors (SSRIs) was recently shown to counteract L-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. However, this effect has never been described in Parkinson's disease (PD) patients, despite that they often receive SSRIs for the treatment of depression. In the present study, we investigated the efficacy of the SSRI citalopram against dyskinesia in two experimental models of PD, the 6-OHDA-lesioned rat and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaque. First, we studied the acute and chronic effect of citalopram, given at different time points before L-DOPA, in L-DOPA-primed parkinsonian rats. Moreover, the acute effect of citalopram was also evaluated in dyskinetic MPTP-treated macaques. In L-DOPA-primed rats, a significant and long-lasting reduction of L-DOPA-induced dyskinesia (LID) was observed only when citalopram was given 30 min before L-DOPA, suggesting that the time of injection relative to L-DOPA is a key factor for the efficacy of the treatment. Interestingly, an acute challenge with the 5-HT1A/1B receptor agonist eltoprazine, given at the end of the chronic study, was equally effective in reducing LID in rats previously chronically treated with L-DOPA or L-DOPA plus citalopram, suggesting that no auto-receptor desensitization was induced by chronic citalopram treatment. In MPTP-treated macaques, citalopram produced a striking suppression of LID but at the expense of L-DOPA therapeutic efficacy, which represents a concern for possible clinical application.
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fidalgo
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Motac Neuroscience, Manchester, UK.
authors.forename: W K D
authors.initials: WK
authors.lastname: Ko
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tronci
authors.affiliation: Motac Neuroscience, Manchester, UK; Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Stancampiano
authors.affiliation: Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chuan
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Motac Neuroscience, Manchester, UK; Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.
authors.forename: E
authors.initials: E
authors.lastname: Bezard
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy. Electronic address: manolocarta@unica.it.
authors.forename: M
authors.initials: M
authors.lastname: Carta
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D015283:Citalopram / Q000627:therapeutic use; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005260:Female; D007980:Levodopa / Q000009:adverse effects*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000188:drug therapy*; D008252:Macaca fascicularis; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D015283:Citalopram; D007980:Levodopa; D016627:Oxidopamine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson’s disease; citalopram; dopamine; dyskinesia; serotonin