The effects of chronic levodopa treatments on the neuronal firing properties of the subthalamic nucleus and substantia nigra reticulata in hemiparkinsonian rhesus monkeys

Abstract

Dopamine replacement therapy with levodopa (LD) is currently the most effective pharmacological treatment for Parkinson's disease (PD), a neurodegenerative disorder characterized by dysfunction of basal ganglia electrophysiology. The effects of chronic LD treatments on the electrophysiological activity of the subthalamic nucleus (STN) and the substantia nigra reticulata (SNR) in parkinsonism are not clear. In the present study we examined the effects of chronic LD treatments on the firing rate and firing pattern of STN and SNR neurons in the stable hemiparkinsonian monkey model of PD. We also evaluated local field potentials of both nuclei before and after LD treatments. In a stable hemiparkinsonian state, STN and SNR had a mean firing rate of 42.6 ± 3.5 Hz (mean ± SEM) and 52.1 ± 5.7 Hz, respectively. Chronic intermittent LD exposure induced marked amelioration of parkinsonism with no apparent drug-induced motor complications. LD treatments did not significantly change the mean firing rate of STN neurons (41.3 ± 3.3 Hz) or bursting neuronal firing patterns. However, LD treatments induced a significant reduction of the mean firing rates of SNR neurons to 36.2 ± 3.3 Hz ( p < 0.05) and a trend toward increased burstiness. The entropy of the spike sequences from STN and SNR was unchanged by LD treatment, while there was a shift of spectral power into higher frequency bands in the LFPs. The inability of chronic LD treatments to reduce the bursty firing patterns in the STN and SNR should be further examined as a potential pathophysiological mechanism for PD symptoms that are refractory to LD treatments.