Long term high frequency stimulation of STN increases dopamine in the corpus striatum of hemiparkinsonian rhesus monkey.
Long term subthalamic nucleus (STN) high frequency stimulation (HFS) can improve most symptoms of Parkinson's disease (PD) patients and decrease the dosage of antiparkinsonian drug such as Madopar. The mechanism of STN HFS for PD still remains elusive. We hypothesize that the level of dopamine (DA) and its metabolites in the corpus striatum is increased after long term STN HFS. The aim of this study was to examine the DA and its metabolites in the extracellular space of corpus striatum in hemiparkinsonian monkeys during long term STN HFS. Four rhesus monkeys were induced to hemiparkinsonian models by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through right internal carotid artery. Then two of them were underwent long term right STN HFS for the subsequent microdialysis sessions. Four microdialysis probe cannulas were implanted into bilateral putamen and caudate nucleus respectively. The microdialysis probe was put into the microdialysis probe cannula of bilateral putamen and caudate nucleus. Dialysates of extracellular space in corpus striatum were collected prior to STN HFS, and subsequently 8 h, 1 week, 1 month, 2 months, 8 months and 10 months after STN HFS. The level of DA and its metabolites were determined by high performance liquid chromatography and subthalamic nucleus electrochemical detection (HPLC-ECD). HFS significantly improved PD symptoms of the monkeys. Rotation evoked by apomorphine (APO) disappeared immediately after HFS pulse generator was turned on. The levels of DA and its metabolites in putamen and caudate nucleus of electrode side increased significantly at different time points after stimulation. Long term STN HFS significantly improved symptoms of hemiparkinsonian rhesus monkey, which might be due to the increase of dopamine and/or its metabolites in corpus striatum.
Zhao
Xu-dong
XD
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 Zhongshan Road, Nanjing 21002, Jiangsu Province, China.
Cao
Yi-qun
YQ
Liu
Han-hua
HH
Li
Feng-qian
FQ
You
Ben-ming
BM
Zhou
Xiao-ping
XP
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D046690:Deep Brain Stimulation; D004298:Dopamine / Q000378:metabolism*; D007150:Immunohistochemistry; D008253:Macaca mulatta; D017551:Microdialysis; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000628:therapy*; D020531:Subthalamic Nucleus / Q000378:metabolism*; D013995:Time
D004298:Dopamine