Division of Molecular Psychiatry (FA, GH), Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
PET Center (VT, AB), Division of Nuclear Medicine, University Hospital, and Center for Radiopharmaceutical Science of ETH, PSI.
Biol Psychiatry. 2016 Mar 15;79(6):474-80. doi: 10.1016/j.biopsych.2015.02.027. Epub 2015 Feb 27.
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.
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.
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%).
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.
尼古丁成瘾是一个主要的公共卫生问题，与初级谷氨酸能功能障碍有关。我们最近发现，吸烟者和近期戒烟者（平均戒断时间为 25 周）的代谢型谷氨酸受体 5（mGluR5）结合明显全球减少。本研究的目的是通过研究一组长期戒烟者（戒断时间>1.5 年），来研究 mGluR5 下调在尼古丁成瘾中的作用，并探讨近期戒烟者中 mGluR5 结合与复发之间的关系。
使用放射性标记的 [11C]ABP688 通过正电子发射断层扫描获得 14 名长期戒烟者的 mGluR5 受体结合图像，该放射性标记物与高特异性的变构位点结合。
长期戒烟者和从未吸烟的个体在所有检查的脑区中 mGluR5 结合均无差异。长期戒烟者的 mGluR5 结合明显高于近期戒烟者，尤其是在额叶皮层（42%）和丘脑（57%）。
我们的研究结果表明，mGluR5 的下调是尼古丁依赖和先前接触尼古丁的个体高复发率的发病机制。因此，mGluR5 受体结合似乎是吸烟的有效生物标志物，也是发现用于尼古丁依赖和其他物质相关障碍的新型药物的有希望的靶点。
