Association of long-term nicotine abstinence with normal metabotropic glutamate receptor-5 binding

Akkus, Funda; Treyer, Valerie; Johayem, Anass; Ametamey, Simon M; Mancilla, Baltazar Gomez; Sovago, Judit; Buck, Alfred; Hasler, Gregor (2016). Association of long-term nicotine abstinence with normal metabotropic glutamate receptor-5 binding. Biological psychiatry, 79(6), pp. 474-480. Elsevier 10.1016/j.biopsych.2015.02.027

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy
04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Healthcare Research

UniBE Contributor:

Akkus, Funda and Hasler, Gregor

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-3223

Publisher:

Elsevier

Language:

English

Submitter:

Gregor Hasler

Date Deposited:

07 Jan 2016 16:06

Last Modified:

06 Feb 2019 11:47

Publisher DOI:

10.1016/j.biopsych.2015.02.027

PubMed ID:

25861697

Uncontrolled Keywords:

Abstinence; Addiction; Glutamate; Nicotine; Relapse mGluR5

BORIS DOI:

10.7892/boris.74434

URI:

https://boris.unibe.ch/id/eprint/74434

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