EFFECTS OF APOMORPHINE ON GLOBUS-PALLIDUS NEURONS IN PARKINSONIAN-PATIENTS

Current hypotheses of basal ganglia dysfunction in Parkinson's disease (PD) propose that neuronal hypoactivity in the globus pallidus extern us (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi,e and GPi,i, re spectively), result in the cardinal symptoms of PD. To test this theor y, the nonselective D-1- and D-2-dopamine receptor agonist apomorphine (30-100 mu g/kg SC) was administered to 14 levodoparesponsive PD pati ents who were off medication (''off' state) while recording neurons in GP. For 15 neurons that were continuously monitored, apomorphine was found to increase the firing rate of 3 neurons in GPe, and decrease th e rate of 12 in GPi. The mean firing rates of many different neurons w ere determined before (n = 285) and at various intervals after (n = 18 4) the injection of the drug. The mean rates before apomorphine were a s follows: GPe, 45 Hz (SD 15, n = 85); GPi,e, 67 Hz (SD 14, n = 125); and GPi,i, 85 Hz (SD 19, n = 75). At 25 to 35 minutes after APO, the r ate of GPe neurons had increased to 72 Hz (SD 18, n = 7), the rate of GPi,e neurons had decreased to 39 Hz (SD 15, n = 15), and in GPi,i the rate decreased to 34 Hz (SD 22, n = 18). Eighty minutes after apomorp hine administration, the mean firing rates returned to preadministrati on values. This study supports current models of basal ganglia dysfunc tion in PD and suggests that the therapeutic effect of apomorphine res ults from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.