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Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia.
Exp Neurol. 2005 Jul; 194(1):66-75.EN

Abstract

Dyskinesia (abnormal involuntary movements) is a common complication of l-DOPA pharmacotherapy in Parkinson's disease, and is thought to depend on abnormal cell signaling in the basal ganglia. Dopamine (DA) denervated mice can exhibit behavioral and cellular signs of dyskinesia when they are treated with l-DOPA, but the clinical relevance of this animal model remains to be established. In this study, we have examined the pharmacological profile of l-DOPA-induced abnormal involuntary movements (AIMs) in the mouse. C57BL/6 mice sustained unilateral injections of 6-hydroxydopamine (6-OHDA) in the striatum. The animals were treated chronically with daily doses of l-DOPA that were sufficient to ameliorate akinetic features without inducing overt signs of dyskinesia upon their first administration. In parallel, other groups of mice were treated with antiparkinsonian agents that do not induce dyskinesia when administered de novo, that is, the D2/D3 agonist ropinirole, and the adenosine A2a antagonist KW-6002. During 3 weeks of treatment, l-DOPA-treated mice developed AIMs affecting the head, trunk and forelimb on the side contralateral to the lesion. These movements were not expressed by animals treated with ropinirole or KW-6002 at doses that improved forelimb akinesia. The severity of l-DOPA-induced rodent AIMs was significantly reduced by the acute administration of compounds that have been shown to alleviate l-DOPA-induced dyskinesia both in parkinsonian patients and in rat and monkey models of Parkinson's disease (amantadine, -47%; buspirone, -46%; riluzole, -33%). The present data indicate that the mouse AIMs are indeed a functional equivalent of l-DOPA-induced dyskinesia.

Authors+Show Affiliations

Wallenberg Neuroscience Centre, Section of Basal Ganglia Pathophysiology, BMC A11, S-221 84 Lund, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

15899244

Citation

Lundblad, M, et al. "Pharmacological Validation of a Mouse Model of l-DOPA-induced Dyskinesia." Experimental Neurology, vol. 194, no. 1, 2005, pp. 66-75.
Lundblad M, Usiello A, Carta M, et al. Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Exp Neurol. 2005;194(1):66-75.
Lundblad, M., Usiello, A., Carta, M., Håkansson, K., Fisone, G., & Cenci, M. A. (2005). Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Experimental Neurology, 194(1), 66-75.
Lundblad M, et al. Pharmacological Validation of a Mouse Model of l-DOPA-induced Dyskinesia. Exp Neurol. 2005;194(1):66-75. PubMed PMID: 15899244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. AU - Lundblad,M, AU - Usiello,A, AU - Carta,M, AU - Håkansson,K, AU - Fisone,G, AU - Cenci,M A, PY - 2004/08/04/received PY - 2005/02/04/revised PY - 2005/02/07/accepted PY - 2005/5/19/pubmed PY - 2005/7/16/medline PY - 2005/5/19/entrez SP - 66 EP - 75 JF - Experimental neurology JO - Exp Neurol VL - 194 IS - 1 N2 - Dyskinesia (abnormal involuntary movements) is a common complication of l-DOPA pharmacotherapy in Parkinson's disease, and is thought to depend on abnormal cell signaling in the basal ganglia. Dopamine (DA) denervated mice can exhibit behavioral and cellular signs of dyskinesia when they are treated with l-DOPA, but the clinical relevance of this animal model remains to be established. In this study, we have examined the pharmacological profile of l-DOPA-induced abnormal involuntary movements (AIMs) in the mouse. C57BL/6 mice sustained unilateral injections of 6-hydroxydopamine (6-OHDA) in the striatum. The animals were treated chronically with daily doses of l-DOPA that were sufficient to ameliorate akinetic features without inducing overt signs of dyskinesia upon their first administration. In parallel, other groups of mice were treated with antiparkinsonian agents that do not induce dyskinesia when administered de novo, that is, the D2/D3 agonist ropinirole, and the adenosine A2a antagonist KW-6002. During 3 weeks of treatment, l-DOPA-treated mice developed AIMs affecting the head, trunk and forelimb on the side contralateral to the lesion. These movements were not expressed by animals treated with ropinirole or KW-6002 at doses that improved forelimb akinesia. The severity of l-DOPA-induced rodent AIMs was significantly reduced by the acute administration of compounds that have been shown to alleviate l-DOPA-induced dyskinesia both in parkinsonian patients and in rat and monkey models of Parkinson's disease (amantadine, -47%; buspirone, -46%; riluzole, -33%). The present data indicate that the mouse AIMs are indeed a functional equivalent of l-DOPA-induced dyskinesia. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15899244/Pharmacological_validation_of_a_mouse_model_of_l_DOPA_induced_dyskinesia_ DB - PRIME DP - Unbound Medicine ER -