Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy)

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Abstract

We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AlMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AlMs in SND and PD rats in a dose-dependent fashion. AlMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AlMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/DeltaFosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance. (C) 2004 Elsevier Inc. All rights reserved.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • rat model, MSA, dyskinesia, motor improvement, levodopa, FosB
Original languageEnglish
Pages (from-to)630-639
JournalNeurobiology of Disease
Volume15
Issue number3
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes