title: Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.
abstract: OBJECTIVE
  Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson's disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.
  
  
  METHODS
  The PD rat model was established by injecting 6-OHDA into the unilateral medial forebrain bundle; while rats were orally pre-treated with simvastatin (1 or 10mg/kg/day), or saline for 5days before surgery, and the same treatments for each group were continued for 3weeks post-surgery. [(3)H] SR141716A binding autoradiography was adopted to investigate the alterations in CB1 receptor density in the brains.
  
  
  RESULTS
  The 6-OHDA induced a remarkable downregulation of CB1 receptor density in the prefrontal cortex, caudate putamen, nucleus accumbens, cingulate cortex, hippocampus, and substantia nigra; while simvastatin (10mg/kg/day) significantly ameliorated this downregulation in those regions. Furthermore, simvastatin (1mg/kg/day) reversed the 6-OHDA-induced downregulation of CB1 receptors in the substantia nigra and hippocampus. Simvastatin showed minimal changes in [(3)H] SR141716A binding in the examined regions in sham rats, but did reveal a significant down-regulation of binding density within the striatum, prefrontal cortex and substantia nigra.
  
  
  CONCLUSIONS
  Alterations in the [(3)H] SR141716A binding in the examined brain areas may represent the specific regions that mediate motor and cognitive dysfunctions in PD via the endocannabinoid system. Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China; Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia; Illawarra Health and Medical Research Institute, NSW 2522, Australia.
authors.forename: Nikolce
authors.initials: N
authors.lastname: Mackovski
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Jinchi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Ruihui
authors.initials: R
authors.lastname: Weng
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia; Illawarra Health and Medical Research Institute, NSW 2522, Australia.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia; Illawarra Health and Medical Research Institute, NSW 2522, Australia.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Meyer
authors.affiliation: Department of Neurosurgery, The University of Texas Medical School at Houston, TX 77030, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia; Illawarra Health and Medical Research Institute, NSW 2522, Australia.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia; Illawarra Health and Medical Research Institute, NSW 2522, Australia. Electronic address: xhuang@uowmail.edu.au.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, People's Republic of China; Centre of Translational Neurosciences, School of Medicine, University of Wollongong, NSW, 2522, Australia. Electronic address: denniswq@yahoo.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D043884:Receptor, Cannabinoid, CB1; D016627:Oxidopamine; D019821:Simvastatin
keywords: 6-hydroxydopamine; Cannabinoid 1 receptor; Parkinson's disease; Simvastatin; [(3)H] SR141716A