Aberrant striatal but not nigral gene expression profiles are specifically associated with dyskinesia behavior following levodopa treatment in the 6-hydroxydopamine lesioned rat

Levodopa-induced dyskinesia (LID) is a common consequence of prolonged pharmacotherapy for Parkinson's disease (PD). While LID becomes more common with long term exposure to levodopa, its development can be quite variable. We leveraged the variable expression of LID in a rat model to interrogate differential gene expression in the substantia nigra and striatum of animals that develop LID and those that do not. Differential expression of genes associated with LID was found only in striatum, not substantia nigra. All rats were unilaterally lesioned using identical parameters with either 6-hydroxydopamine or vehicle lesion. Success was determined by >90% reduction of DA in the striatum as measured by HPLC, and behaviorally using non-drugged motor behavior testing. Daily injections of levodopa or saline were commenced 3.5 weeks after 6-OHDA lesioning. LID behaviors were rated every other day for a total of seven sessions.