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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Erwan Bezard
  • Ana Munoz
  • Elisabetta Tronci
  • Elsa Y. Pioli
  • Qin Li
  • Gregory Porras
  • Anders Björklund
  • Manolo Carta
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)242-246
TidskriftNeuroscience Research
Volym77
Utgåva nummer4
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa