Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson’s disease

C. Fidalgo, W.K.D. Ko, E. Tronci, Q. Li, R. Stancampiano, Q. Chuan, E. Bezard, M. Carta
Neuroscience. 2015-07-01; 298: 389-396
DOI: 10.1016/j.neuroscience.2015.04.027

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1. Neuroscience. 2015 Jul 9;298:389-96. doi: 10.1016/j.neuroscience.2015.04.027.
Epub 2015 Apr 20.

Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal
models of Parkinson’s disease.

Fidalgo C(1), Ko WK(2), Tronci E(1), Li Q(3), Stancampiano R(1), Chuan Q(4),
Bezard E(5), Carta M(6).

Author information:
(1)Department of Biomedical Sciences, Section of Physiology, University of
Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy.
(2)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.
(3)Motac Neuroscience, Manchester, UK; Institute of Lab Animal Sciences, China
Academy of Medical Sciences, Beijing, China.
(4)Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing,
China.
(5)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.
(6)Department of Biomedical Sciences, Section of Physiology, University of
Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy. Electronic
address: .

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.

Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuroscience.2015.04.027
PMID: 25907446 [Indexed for MEDLINE]

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