Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate Receptor-5 Binding
DOKPE
- Akkus, Funda University of Bern, Switzerland
- Treyer, Valerie Center for Radiopharmaceutical Science of ETH, Villigen PSI, Switzerland
- Johayem, Anass ETH, Zurich, Switzerland
- Ametamey, Simon M. ETH, Zurich, Switzerland
- Gomez Mancilla, Baltazar Novartis Pharma AG, Basel, Switzerland
- Sovago, Judit Novartis Pharma AG, Basel, Switzerland
- Buck, Alfred Center for Radiopharmaceutical Science of ETH, Villigen PSI, Switzerland
- Hasler, Gregor ORCID [University of Fribourg] ; University of Bern, Switzerland
- 2016
Published in:
- Biological Psychiatry. - Amsterdam : Elsevier BV. - 2016, vol. 79, no. 6, p. 474-480
English
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.
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Master en médecine
- Language
-
- English
- Classification
- Pathology, clinical medicine
- License
- Rights reserved
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.biopsych.2015.02.027
- ISSN 0006-3223
- Persistent URL
- https://folia.unifr.ch/unifr/documents/327577
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