Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracellular striatal dopamine.
Since electrophysiological correlates of L-dopa-induced dyskinesia (LID) are almost unknown, changes of striatal dopamine (DA) transmission and electrophysiological activity of the substantia nigra pars reticulata (SNr) were recorded before and after acute L-dopa administration in sham-operated and 6-hydroxydopamine (6-OHDA)-lesioned rats that were previously treated with vehicle or L-dopa for 10 days. Abnormal involuntary movements occurred only in the L-dopa-primed 6-OHDA-lesioned rats that showed after acute l-dopa administration a decrease in firing rate, the highest local field potential power in the theta/alpha band, a consequent oscillatory activity in the same frequency band at the single neuron level and an excessive increase in striatal DA release associated with the lowest level of DA metabolism. These results suggest that increased synchronised afferent activity may drive SNr oscillations in the same frequency band and is associated with abnormal involuntary movements, further suggesting the potential use of desynchronising drugs for managing LID in Parkinson's disease.
Meissner
Wassilios
W
Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, CNRS UMR 5543, Université Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Ravenscroft
Paula
P
Reese
René
R
Harnack
Daniel
D
Morgenstern
Rudolf
R
Kupsch
Andreas
A
Klitgaard
Henrik
H
Bioulac
Bernard
B
Gross
Christian E
CE
Bezard
Erwan
E
Boraud
Thomas
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology; D020820:Dyskinesias / Q000209:etiology* / Q000503:physiopathology; D045604:Extracellular Fluid / Q000737:chemistry; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology*
D018663:Adrenergic Agents; D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid