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 externus (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi,e and GPi,i, respectively), result in the cardinal symptoms of PD. To test this theory, the nonselective D1- and D2-dopamine receptor agonist apomorphine (30-100 microg/kg SC) was administered to 14 levodopa-responsive PD patients 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 the rate of 12 in GPi. The mean firing rates of many different neurons were determined before (n = 285) and at various intervals after (n = 184) the injection of the drug. The mean rates before apomorphine were as 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 rate 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 apomorphine administration, the mean firing rates returned to preadministration values. This study supports current models of basal ganglia dysfunction in PD and suggests that the therapeutic effect of apomorphine results from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.
Hutchinson
W D
WD
Department of Surgery, Toronto Hospital (Western Division), Ontario, Canada.
Levy
R
R
Dostrovsky
J O
JO
Lozano
A M
AM
Lang
A E
AE
D000200:Action Potentials / Q000502:physiology; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001058:Apomorphine / Q000008:administration & dosage*; D004594:Electrophysiology; D005917:Globus Pallidus / Q000166:cytology* / Q000187:drug effects / Q000601:surgery; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D000978:Antiparkinson Agents; D001058:Apomorphine