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

Summary, in English

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.

• Author: N Stefanova; Martin Lundblad; F Tison; W Poewe; Angela Cenci Nilsson; GK Wenning
• Department/s: Basal Ganglia Pathophysiology
• Publishing year: 2004
• Language: English
• Pages: 630-639
• Publication/Series: Neurobiology of Disease
• Volume: 15
• Issue: 3
• Links: http://dx.doi.org/10.1016/j.nbd.2003.11.025
• Document type: Journal article
• Publisher: Elsevier
• Topic: Neurosciences
• Keywords: rat model; MSA; dyskinesia; motor improvement; levodopa; FosB
• Status: Published
• Research group: Basal Ganglia Pathophysiology
• ISBN/ISSN/Other: ISSN: 0969-9961