Effects of apomorphine on subthalamic nucleus and globus pallidus internusneurons in patients with Parkinson's disease

This study examines the effect of apomorphine (APO), a nonselective D-1- an d D-2-dopamine receptor agonist, on the firing activity of neurons in the s ubthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) in patients with Parkinson's disease (PD). Single-unit microelectrode recor dings were conducted in 13 patients undergoing implantation of deep brain s timulation electrodes in STN and 6 patients undergoing a pallidotomy. Doses of APO (2.5-8 mg) were sufficient to produce an ON state, but not intended to induce dyskinetic movements. Following baseline recordings from a singl e neuron, APO was administered and the activity of the neuron followed for an average of 15 min. The spontaneous discharge of neurons encountered befo re (n = 309), during (n = 146, 10-60 min), and after the effect of APO had waned (n = 127, >60 min) was also sampled, and the response to passive join t movements was noted. In both nuclei, APO increased the overall proportion of spikes in burst discharges (as detected with Poisson "surprise" analysi s), and a greater proportion of cells with an irregular discharge pattern w as observed. APO significantly decreased the overall firing rates of GPi ne urons (P< 0.01), but there was no change in the overall firing rate of neur ons in the STN (P = 0.68). However, the mean firing rates of STN neurons du ring APO-induced movements (choreic or dystonic dyskinesias) that occurred in four patients were significantly lower than OFF-period baseline values ( P<0.05). Concurrent with a reduction in limb tremor, the percentage of cell s with tremor-related activity (TCs) was found to be significantly reduced from 19 to 6% in the STN and 14 to 0% in the GPi following APO administrati on. APO also decreased the firing rate of STN TCs (P< 0.05). During the OFF state, more than 15% of neurons tested (STN = 93, GPi = 63) responded to p assive movement of two or more joints. After APO, this proportion decreased significantly to 7% of STN cells and 4% of GPi cells (STN = 28, GPi = 26). These findings suggest that the APO-induced amelioration of parkinsonian s ymptoms is not solely due to a decrease in overall activity in the GPi or S TN as predicted by the current model of basal ganglia function in PD.