Format

Send to

Choose Destination
Biol Psychiatry. 2016 Mar 15;79(6):474-80. doi: 10.1016/j.biopsych.2015.02.027. Epub 2015 Feb 27.

Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate Receptor-5 Binding.

Author information

1
Division of Molecular Psychiatry (FA, GH), Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
2
PET Center (VT, AB), Division of Nuclear Medicine, University Hospital, and Center for Radiopharmaceutical Science of ETH, PSI.
3
Department of Chemistry and Applied Biosciences of ETH (AJ, SMA), USZ, Zurich, Switzerland.
4
Novartis Institute for BioMedical Research (BGM, JS), Novartis Pharma AG, Basel, Switzerland.
5
Division of Molecular Psychiatry (FA, GH), Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland. Electronic address: g.hasler@bluewin.ch.

Abstract

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.

KEYWORDS:

Abstinence; Addiction; Glutamate; Nicotine; Relapse; mGluR5

PMID:
25861697
DOI:
10.1016/j.biopsych.2015.02.027
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center