Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy).
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/Delta FosB 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.
Stefanova
N
N
Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria.
Lundblad
M
M
Tison
F
F
Poewe
W
W
Cenci
M A
MA
Wenning
G K
GK
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020820:Dyskinesias / Q000188:drug therapy*; D005552:Forelimb / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D020955:Striatonigral Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000978:Antiparkinson Agents; D007980:Levodopa