Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate Receptor-5 Binding
| Autor: | Simon M. Ametamey, Gregor Hasler, Alfred Buck, Baltazar Gomez Mancilla, Anass Johayem, Valerie Treyer, Judit Sovago, Funda Akkus |
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| Přispěvatelé: | University of Zurich, Hasler, Gregor |
| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Adult Male Pyridines media_common.quotation_subject Receptor Metabotropic Glutamate 5 Allosteric regulation 610 Medicine & health Pharmacology Nicotine 03 medical and health sciences Glutamatergic 0302 clinical medicine Recurrence mental disorders Oximes medicine Humans Carbon Radioisotopes Biological Psychiatry media_common Metabotropic glutamate receptor 5 Addiction Smoking Glutamate receptor Brain 10181 Clinic for Nuclear Medicine Tobacco Use Disorder Abstinence Middle Aged Magnetic Resonance Imaging 030104 developmental biology nervous system Metabotropic glutamate receptor Positron-Emission Tomography Female Psychology 2803 Biological Psychiatry 030217 neurology & neurosurgery Biomarkers medicine.drug |
| Zdroj: | Biological psychiatry. 79(6) |
| ISSN: | 1873-2402 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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