Akkus, FundaFundaAkkusTreyer, ValerieValerieTreyerJohayem, AnassAnassJohayemAmetamey, Simon MSimon MAmetameyMancilla, Baltazar GomezBaltazar GomezMancillaSovago, JuditJuditSovagoBuck, AlfredAlfredBuckHasler, GregorGregorHasler0000-0002-8311-01382024-10-232024-10-232016https://boris-portal.unibe.ch/handle/20.500.12422/136925BACKGROUND 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.enAbstinenceAddictionGlutamateNicotineRelapse mGluR5600 - Technology::610 - Medicine & healtharticle10.7892/boris.744342586169710.1016/j.biopsych.2015.02.027