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

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Author

  • Erwan Bezard
  • Ana Munoz
  • Elisabetta Tronci
  • Elsa Y. Pioli
  • Qin Li
  • Gregory Porras
  • Anders Björklund
  • Manolo Carta

Summary, in English

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.

Publishing year

2013

Language

English

Pages

242-246

Publication/Series

Neuroscience Research

Volume

77

Issue

4

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Keywords

  • Dyskinesia
  • L-DOPA
  • Parkinson's disease
  • 6-OHDA
  • Serotonin
  • 5-HT1A/1B
  • agonists

Status

Published

Research group

  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 0168-0102