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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 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
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
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
2014-02-10 12:14:20
date last changed
2019-02-20 05:51:13
@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},
  keyword      = {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},
  volume       = {77},
  year         = {2013},
}