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

Neurobiology of Disease

M Lundblad¹  M.A Cenci¹  F Tison²  G.K Wenning²  N Stefanova³  W Poewe³ 

[1] Department of Physiological Sciences, Neurobiology Division, Wallenberg Neuroscience Center, University of Lund, Lund, Sweden;Laboratoire de Neurophysiologie, UMR-CNRS 5543-Universite Victor Segalen Bordeux2, Bordeaux, France;Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria;

关键词: Dyskinesia;    Motor improvement;    MSA;    Rat model;    Levodopa;    FosB;   

DOI  :  

来源: DOAJ

【 摘 要 】

We examined the role of a striatal lesion in the development of l-DOPA-induced abnormal involuntary movements (AIMs) 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 AIMs in SND and PD rats in a dose-dependent fashion. AIMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AIMs 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/ΔFosB 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.

【 授权许可】

Unknown