title: Additional noradrenergic depletion aggravates forelimb akinesia and abnormal subthalamic nucleus activity in a rat model of Parkinson's disease.
abstract: OBJECTIVE
  This study aims to identify the contribution of additional noradrenergic depletion to forelimb akinesia and abnormal subthalamic nucleus (STN) firing activity in Parkinson's disease (PD).
  
  
  METHODS
  Forelimb akinesia behaviors were tested in awake rats with noradrenergic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions, unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra pars compacta (SNc) and with combined 6-OHDA and DSP-4 lesions. STN extracellular single-unit and local field potential (LFP) activities were examined in the animals that were anesthetized with urethane.
  
  
  RESULTS
  The adjusting steps and the contralateral touches of rats in the forelimb akinesia behavior tests were markedly inhibited by a further noradrenergic lesion with DSP-4 in 6-OHDA+DSP-4-lesioned group when compared with those of 6-OHDA-lesioned animals (P<0.05 for all comparisons). Meanwhile, the neuronal firing pattern of STN also changed significantly towards more bursty in 6-OHDA + DSP-4-lesioned group (P <0 .05). Compared with 6-OHDA-lesioned animals, an additional noradrenergic lesion increased the 0.3-2.5 Hz oscillatory activity and the spike power of STN neurons (P < 0.01 for both comparisons), and strengthened the synchronized oscillation between subthalamic neuronal firing and LFP activity in 6-OHDA + DSP-4-lesioned group (P < 0.01).
  
  
  CONCLUSIONS
  The results provide evidence to support the correlation between noradrenergic depletion and the further exaggerated dysfunction of STN electrical activity in PD and suggest that an aberrant noradrenergic system might play a specific role in the motor deficits of PD.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yi Na
authors.initials: YN
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Environment and Disease-Related Genes, Ministry of Education, Xi'an 710061, China.
authors.forename: Ling Na
authors.initials: LN
authors.lastname: Han
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Li Bo
authors.initials: LB
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Zhong Heng
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Environment and Disease-Related Genes, Ministry of Education, Xi'an 710061, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000200:Action Potentials; D000818:Animals; D001596:Benzylamines; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D005552:Forelimb / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats / Q000502:physiology; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001596:Benzylamines; D016627:Oxidopamine; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine
keywords: Akinesia; Firing pattern; Norepinephrine; Oscillatory activity; Parkinson's disease; Subthalamic nucleus