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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Erwan Bezard
  • Ana Munoz
  • Elisabetta Tronci
  • Elsa Y. Pioli
  • Qin Li
  • Gregory Porras
  • Anders Björklund
  • Manolo Carta
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Dyskinesia, L-DOPA, Parkinson's disease, 6-OHDA, Serotonin, 5-HT1A/1B, agonists
Original languageEnglish
Pages (from-to)242-246
JournalNeuroscience Research
Volume77
Issue number4
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes