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A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function
Open accessAbstract
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.
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Citations
Cites
Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia
Picconi, B., Centonze, D., Håkansson, K., Bernardi, G., Greengard, P., Fisone, G., Cenci, M. A., & Calabresi, P. (2003) · Nature Neuroscience · doi:10.1038/nn1040 · Cited by 821
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Cited by
Toxin-induced models of Parkinson’s disease
Bové, J., Prou, D., Perier, C., & Przedborski, S. (2005) · NeuroRX · doi:10.1602/neurorx.2.3.484 · Cited by 739
Santini, E., Valjent, E., Usiello, A., Carta, M., Borgkvist, A., Girault, J.-A., Herve, D., Greengard, P., & Fisone, G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0852-07.2007 · Cited by 437
Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors
Bateup, H. S., Santini, E., Shen, W., Birnbaum, S., Valjent, E., Surmeier, D. J., Fisone, G., Nestler, E. J., & Greengard, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009874107 · Cited by 360
Fieblinger, T., Graves, S. M., Sebel, L. E., Alcacer, C., Plotkin, J. L., Gertler, T. S., Chan, C. S., Heiman, M., Greengard, P., Cenci, M. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6316 · Cited by 295
Self-citationDarmopil, S., Martín, A. B., De Diego, I. R., Ares, S., & Moratalla, R. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.04.025 · Cited by 271
Metadata
- Authors
- Lundblad, M., Picconi, B., Lindgren, H., & Cenci, M. A.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 16
- Issue
- 1
- Pages
- 110-123
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2062319694
- Cited by
- 330
- References
- 1
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Lundblad, M., Picconi, B., Lindgren, H., & Cenci, M. A. (2004). A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2004.01.007
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