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

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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; Carta, Manolo.

I: Neuroscience Research, Vol. 77, Nr. 4, 2013, s. 242-246.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Bezard, E, Munoz, A, Tronci, E, Pioli, EY, Li, Q, Porras, G, Björklund, A & Carta, M 2013, 'Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia', Neuroscience Research, vol. 77, nr. 4, s. 242-246. https://doi.org/10.1016/j.neures.2013.10.002

APA

Bezard, E., Munoz, A., Tronci, E., Pioli, E. Y., Li, Q., Porras, G., ... Carta, M. (2013). Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia. Neuroscience Research, 77(4), 242-246. https://doi.org/10.1016/j.neures.2013.10.002

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Author

Bezard, Erwan ; Munoz, Ana ; Tronci, Elisabetta ; Pioli, Elsa Y. ; Li, Qin ; Porras, Gregory ; Björklund, Anders ; Carta, Manolo. / Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia. I: Neuroscience Research. 2013 ; Vol. 77, Nr. 4. s. 242-246.

RIS

TY - JOUR

T1 - Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia

AU - Bezard, Erwan

AU - Munoz, Ana

AU - Tronci, Elisabetta

AU - Pioli, Elsa Y.

AU - Li, Qin

AU - Porras, Gregory

AU - Björklund, Anders

AU - Carta, Manolo

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Dyskinesia

KW - L-DOPA

KW - Parkinson's disease

KW - 6-OHDA

KW - Serotonin

KW - 5-HT1A/1B

KW - agonists

U2 - 10.1016/j.neures.2013.10.002

DO - 10.1016/j.neures.2013.10.002

M3 - Article

VL - 77

SP - 242

EP - 246

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

IS - 4

ER -