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Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia

Bezard, Erwan ; Munoz, Ana ; Tronci, Elisabetta ; Pioli, Elsa Y. ; Li, Qin ; Porras, Gregory ; Björklund, Anders LU orcid and Carta, Manolo (2013) In Neuroscience Research 77(4). p.242-246
Abstract
The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract LDOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline... (More)
The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract LDOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0 mg/kg). At a lower dose (0.75 mg/ kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease. (c) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dyskinesia, L-DOPA, Parkinson's disease, 6-OHDA, Serotonin, 5-HT1A/1B, agonists
in
Neuroscience Research
volume
77
issue
4
pages
242 - 246
publisher
Elsevier
external identifiers
  • wos:000328922900008
  • scopus:84888362340
  • pmid:24135129
ISSN
0168-0102
DOI
10.1016/j.neures.2013.10.002
language
English
LU publication?
yes
id
11301240-e8cd-4966-bd03-ebf892fa4b41 (old id 4258968)
date added to LUP
2016-04-01 13:42:13
date last changed
2022-03-06 07:17:23
@article{11301240-e8cd-4966-bd03-ebf892fa4b41,
  abstract     = {{The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract LDOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0 mg/kg). At a lower dose (0.75 mg/ kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease. (c) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.}},
  author       = {{Bezard, Erwan and Munoz, Ana and Tronci, Elisabetta and Pioli, Elsa Y. and Li, Qin and Porras, Gregory and Björklund, Anders and Carta, Manolo}},
  issn         = {{0168-0102}},
  keywords     = {{Dyskinesia; L-DOPA; Parkinson's disease; 6-OHDA; Serotonin; 5-HT1A/1B; agonists}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{242--246}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience Research}},
  title        = {{Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia}},
  url          = {{http://dx.doi.org/10.1016/j.neures.2013.10.002}},
  doi          = {{10.1016/j.neures.2013.10.002}},
  volume       = {{77}},
  year         = {{2013}},
}