Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4258968
- author
- Bezard, Erwan ; Munoz, Ana ; Tronci, Elisabetta ; Pioli, Elsa Y. ; Li, Qin ; Porras, Gregory ; Björklund, Anders LU and Carta, Manolo
- organization
- publishing date
- 2013
- 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
- pmid:24135129
- 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
- 2016-04-01 13:42:13
- date last changed
- 2022-03-06 07:17:23
@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}}, keywords = {{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}}, doi = {{10.1016/j.neures.2013.10.002}}, volume = {{77}}, year = {{2013}}, }