title: Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy).
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Stefanova
authors.forename: M
authors.initials: M
authors.lastname: Lundblad
authors.forename: F
authors.initials: F
authors.lastname: Tison
authors.forename: W
authors.initials: W
authors.lastname: Poewe
authors.forename: M A
authors.initials: MA
authors.lastname: Cenci
authors.forename: G K
authors.initials: GK
authors.lastname: Wenning
mesh_terms: 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
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa