title: Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate Receptor-5 Binding.
abstract: BACKGROUND
  Nicotine addiction is a major public health problem and is associated with primary glutamatergic dysfunction. We recently showed marked global reductions in metabotropic glutamate receptor type 5 (mGluR5) binding in smokers and recent ex-smokers (average abstinence duration of 25 weeks). The goal of this study was to examine the role of mGluR5 downregulation in nicotine addiction by investigating a group of long-term ex-smokers (abstinence >1.5 years), and to explore associations between mGluR5 binding and relapse in recent ex-smokers.
  
  
  METHODS
  Images of mGluR5 receptor binding were acquired in 14 long-term ex-smokers, using positron emission tomography with radiolabeled [11C]ABP688, which binds to an allosteric site with high specificity.
  
  
  RESULTS
  Long-term ex-smokers and individuals who had never smoked showed no differences in mGluR5 binding in any of the brain regions examined. Long-term ex-smokers showed significantly higher mGluR5 binding than recent ex-smokers, most prominently in the frontal cortex (42%) and thalamus (57%).
  
  
  CONCLUSIONS
  Our findings suggest that downregulation of mGluR5 is a pathogenetic mechanism underlying nicotine dependence and the high relapse rate in individuals previously exposed to nicotine. Therefore, mGluR5 receptor binding appears to be an effective biomarker in smoking and a promising target for the discovery of novel medication for nicotine dependence and other substance-related disorders.
authors: Division of Molecular Psychiatry (FA, GH), Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
authors: Funda
authors: F
authors: Akkus
authors: PET Center (VT, AB), Division of Nuclear Medicine, University Hospital, and Center for Radiopharmaceutical Science of ETH, PSI.
authors: Valerie
authors: V
authors: Treyer
authors: Department of Chemistry and Applied Biosciences of ETH (AJ, SMA), USZ, Zurich, Switzerland.
authors: Anass
authors: A
authors: Johayem
authors: Department of Chemistry and Applied Biosciences of ETH (AJ, SMA), USZ, Zurich, Switzerland.
authors: Simon M
authors: SM
authors: Ametamey
authors: Novartis Institute for BioMedical Research (BGM, JS), Novartis Pharma AG, Basel, Switzerland.
authors: Baltazar Gomez
authors: BG
authors: Mancilla
authors: Novartis Institute for BioMedical Research (BGM, JS), Novartis Pharma AG, Basel, Switzerland.
authors: Judit
authors: J
authors: Sovago
authors: PET Center (VT, AB), Division of Nuclear Medicine, University Hospital, and Center for Radiopharmaceutical Science of ETH, PSI.
authors: Alfred
authors: A
authors: Buck
authors: Division of Molecular Psychiatry (FA, GH), Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland. Electronic address: g.hasler@bluewin.ch.
authors: Gregor
authors: G
authors: Hasler
mesh_terms: D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010091:Oximes / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012008:Recurrence; D012907:Smoking / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D015415:Biomarkers; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
keywords: Abstinence; Addiction; Glutamate; Nicotine; Relapse; mGluR5