Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates Parkinson's disease (PD) symptoms. Although widely used, the mechanisms of action are still unknown. In an attempt to elucidate those mechanisms, we have previously demonstrated that STN-DBS increases striatal extracellular dopamine (DA) metabolites in anaesthetized rats. PD being a movement disorder, it remains to be determined whether these findings are related to any relevant motor or behavioural changes. Thus, this study investigates concomitant behavioural changes during STN-DBS and extracellular striatal DA metabolites measured using microdialysis in freely moving 6-hydroxydopamine-lesioned rats. STN-DBS induced an increase of striatal DA metabolites in awake, freely moving animals. Furthermore, we observed concomitant contralateral circling behaviour. Taken together, these results suggest that STN-DBS could disinhibit (consequently activate) substantia nigra compacta neurons via inhibition of gamma-aminobutyric acid-ergic substantia nigra reticulata neurons.
Department of Neurology, Charité Campus Virchow-Klinikum, Humboldt-University Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Wassilios
W
Meissner
Daniel
D
Harnack
Gesine
G
Paul
Torsten
T
Reum
Reinhard
R
Sohr
Rudolf
R
Morgenstern
Andreas
A
Kupsch
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004599:Electric Stimulation Therapy; D007839:Functional Laterality / Q000502:physiology; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D013565:Sympatholytics / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine