P 71 Levodopa modulates beta and gamma oscillations in the cortico-basal ganglia loop with a higher efficacy than the dopamine receptor agonist apomorphine in experimental Parkinsonism

Abstract

The pharmacotherapy of Parkinson’s disease (PD) is based on levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents provide beneficial clinical effects on motor and non-motor symptoms in PD clinical efficiency and side effects differ substantially between levodopa and dopamine receptor agonists. Levodopa is known to provide a greater symptomatic relief than dopamine receptor agonists. Since long-term levodopa treatment often results in debilitating motor fluctuations, dopamine receptor agonists are recommended in younger patients. The pharmacodynamic basis of these profound differences is not understood so far. Levodopa and dopamine receptor agonists may have a different impact on beta and gamma oscillations in the cortico-basal ganglia loop that have been shown to be of importance for the pathophysiology of PD. We performed in vivo electrophysiological recordings in anesthetized dopamine-intact and dopamine-depleted rats compare the impact of levodopa or apomorphine on neuronal population oscillations. Our results demonstrated that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations that are often associated with bradykinesia while simultaneously increasing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit.