title: Blockade of mGluR5 reverses abnormal firing of subthalamic nucleus neurons in 6-hydroxydopamine partially lesioned rats.
abstract: Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic nucleus (STN) results in burst-firing activity of STN neurons, which is similar to that observed in Parkinson's disease (PD). We examined the effects of chronic and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, in firing activity of STN neurons in partially lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in vehicle-treated rats showed an increasing firing rate and a more irregular firing pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, 14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats. These data demonstrate that partial lesion of the nigrostriatal pathway increases firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment has the neuroprotective effect and reverses the abnormal firing activity of STN neurons, suggesting that MPEP has an important implication for the treatment of PD.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Umar
authors.initials: U
authors.lastname: Ali
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Gui
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Hou
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Fan
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016627:Oxidopamine; D011725:Pyridines; D018092:Kainic Acid Receptors; D014446:Tyrosine 3-Monooxygenase; C121465:6-methyl-2-(phenylethynyl)pyridine