Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias.
The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi of parkinsonian monkeys continuously through the "off" and "on" states, and 10 to 15 minutes later during "on with or without dyskinesias," depending on two doses of levodopa. The transition from the "off" to the "on" state was characterized by a decrease (most cells), no change, or an increase in firing rate of individual cells. During dyskinesias, firing rates declined profoundly in almost all cells, with decrements as low as 97% in individual cells. These changes occurred only when dyskinesias were present. The difference in GPi activity between "on" and "on with dyskinesias" suggests that normal motor function in Parkinson's disease critically depends on fine tuning of the basal ganglia output. Dyskinesias result from an imbalanced low GPi discharge, a circumstance that may be susceptible to development of new therapeutic approaches.
Papa
S M
SM
Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD, USA.
Desimone
R
R
Fiorani
M
M
Oldfield
E H
EH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use / Q000633:toxicity; D002230:Carbidopa / Q000627:therapeutic use* / Q000633:toxicity*; D004338:Drug Combinations; D004409:Dyskinesia, Drug-Induced; D020820:Dyskinesias / Q000503:physiopathology*; D004594:Electrophysiology / Q000379:methods; D005133:Eye Movements; D005917:Globus Pallidus / Q000187:drug effects* / Q000503:physiopathology; D007980:Levodopa / Q000627:therapeutic use* / Q000633:toxicity*; D008253:Macaca mulatta; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*
D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002230:Carbidopa