Objective: To clarify the role of pathologic oscillations in Parkinson’s disease (PD) we recorded local field potentials (LFPs) in cortico-basal ganglia circuits of Parkinsonian and control rats under the influence of different doses of dopaminergic stimulation.

Background: Pathologic oscillations seem to play a paramount role in the pathophysiology of PD. While excessive synchronized beta activity in the cortico-basal ganglia circuit is hypothesized to contribute to motor impairment, recent studies indicate that gamma activity may be prokinetic and that it might be reduced in PD.

Methods: We simultaneously recorded LFPs from the primary motor cortex, subthalamic nucleus and substantia nigra pars reticulata in 6-OHDA-lesioned rats (n=42) and in dopamine-intact controls (n=21) under urethane anaesthesia. After a baseline recording, we administered dopaminergic medication and repeated measurements after each application. We either injected three successive doses of levodopa (6, 12, 24 mg/kg) or apomorphine (0.05, 0.1, 0.2 mg/kg) or one singular dose of levodopa (24 mg/kg) combined with either raclopride (D2 receptor antagonist, 1 mg/kg) or SCH 2390 (D1 receptor antagonist, 0.5 mg/kg). We calculated power spectral densities and coherence using custom written Matlab scripts.

Results: Beta-oscillations (13-30 Hz) in lesioned animals were dose dependently suppressed by levodopa while a distinct gamma peak appeared at approximately 65 Hz that further increased with higher doses. The maximal increase in gamma oscillations was more pronounced in controls. Similar observations could be made under apomorphine administration. When combining levodopa with a D1 receptor antagonist the effects on beta and gamma activity were comparable to but smaller than those of non-selective dopaminergic stimulation. Blockage of D2 dopamine receptors before levodopa application led to a less pronounced suppression of beta oscillations and no distinct changes in gamma band activity.

Conclusions: Our findings indicate that dopaminergic medication has opposite effects on beta- and gamma-oscillations in cortico-basal ganglia circuits which seem to be promoted predominantly via D2 dopamine receptors. Furthermore, higher activation levels in the gamma band in dopamine-intact controls with and without dopaminergic stimulation suggest that gamma oscillations could be considered as physiological.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-impact-of-levodopa-and-apomorphine-on-beta-and-gamma-oscillations-in-cortico-basal-ganglia-circuits-in-experimental-parkinsonism/