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A model of L-DOPA-i...
A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function.
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- Lundblad, Martin (author)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
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Picconi, B (author)
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- Lindgren, Hanna (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Cenci Nilsson, Angela (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Neuronano Research Center (NRC),Basal Ganglia Pathophysiology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 16:1, s. 110-123
- Related links:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- L-DOPA-induced dyskinesia is a major complication of L-DOPA pharmacotherapy in Parkinson's disease, and is thought to depend on abnormal cell signaling in the basal ganglia. In this study, we have addressed the possibility to model L-DOPA-induced dyskinesia in the mouse at both the behavioral and the molecular level. C57BL/6 mice sustained unilateral injections of 6-hydroxydopamine (6-OHDA) either in the medial forebrain bundle (MFB) or in the sensorimotor part of the striatum. Both types of lesion produced a similar degree of forelimb akinesia on the contralateral side of the body. The lowest dose of L-DOPA that could significantly relieve this akinetic deficit (i.e., 6 mg/kg) did not differ between MFB and intrastriatal lesions. The L-DOPA threshold dose for the induction of dyskinesia did however differ between the two lesion types. A daily dose of 6 mg/kg L-DOPA caused MFB lesioned mice to develop abnormal movements affecting orofacial, trunk, and forelimb muscles on the side contralateral to the lesion, whereas a daily dose of 18 mg/kg was required to produce comparable dyskinetic effects in the intrastriatally lesioned animals. The development of abnormal movements was accompanied by a striatal induction of DeltaFosB-like proteins and prodynorphin mRNA, that is, molecular markers that are associated with L-DOPA-induced dyskinesia in both rats and nonhuman primates. We conclude that 6-OHDA lesioned mice exhibit behavioral and cellular features of akinesia and L-DOPA-induced dyskinesia that are similar to those previously characterized in rats. The mouse model of L-DOPA-induced dyskinesia will provide a useful tool to study the molecular determinants of this movement disorder in transgenic mice strains.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- L-DOPA
- Cellular parameter
- Nigrostriatal function
Publication and Content Type
- art (subject category)
- ref (subject category)
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