Akkus, Funda Treyer, Valerie Johayem, Anass Ametamey, Simon M. Gomez Mancilla, Baltazar Sovago, Judit Buck, Alfred Hasler, Gregor 2016 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. application/pdf https://folia.unifr.ch/global/documents/327577 https://folia.unifr.ch/documents/327577/files/akkusetal.2016.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopsych.2015.02.027 info:eu-repo/semantics/altIdentifier/issn/0006-3223 info:eu-repo/semantics/openAccess Rights reserved Biological Psychiatry. - Amsterdam : Elsevier BV. - 2016, vol. 79, no. 6, p. 474-480 Abstinence Addiction Glutamate Nicotine Relapse mGluR5 info:eu-repo/classification/udc/616 Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate Receptor-5 Binding http://purl.org/coar/resource_type/c_6501