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/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.

Keywords

• Dyskinesia
• Motor improvement
• MSA
• Rat model
• Levodopa
• FosB