L-DOPA Rescues Reach Height but Not Trajectory Area in a Bimanual String-Pulling Behavior in Parkinsonian Rats

Abstract

While gross motor changes in Parkinson's disease, bradykinesia, hypokinesia, difficulty initiating movement, have been well studied in rodent models of the disease, limb movements, and especially bimanual coordination deficits, are more difficult to study in these animal models. Here we describe a novel bimanual string-pulling task that can be used to generate a rich repertoire of behaviors that require limb and bimanual coordination in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion. We show that 6-OHDA lesion significantly reduces string speed, pulling bout duration, paw speed especially during reaching, and reduces the area of paw trajectories during pulling. However, it does not affect the variability around that movement trajectory. We also show that levodopa (L-DOPA) treatment restores many of these measures but not all. L-DOPA restores paw speed and string-pulling speed and fully restores paw reach height and pulling bout duration, but has no effect on trajectory area. Together, our results demonstrate that dopamine depletion differentially effects features of this bimanual coordination task, that L-DOPA mostly, but not fully, restores string pulling performance, and opens up a new avenue for measuring the effect of Parkinson's disease treatments on motor movement, allowing for better assessment of how effectively treatments restore motor activity.