History of cigarette smoking is associated with higher limbic GABA_A receptor availability

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• 作者：Paul R.A. Stokes^a ; ^{paul.stokes@imperial.ac.uk} ; Aaf Benecke^a ; ^e ; Jim Myers^b ; David Erritzoe^a ; Ben J. Watson^b ; Nicola Kalk^a ; Daniela Riano Barros^c ; Alexander Hammers^c ; ^d ; David J. Nutt^a ; Anne R. Lingford-Hughes^a
• 关键词：Nicotine ; PET ; GABA ; [11C]Ro15 4513 ; Addiction ; Limbic
• 刊名：NeuroImage
• 出版年：2013
• 出版时间：1 April, 2013
• 年：2013
• 卷：69
• 期：Complete
• 页码：70-77
• 全文大小：441 K

文摘

Cigarette smoking presents a significant worldwide healthcare challenge. Preclinical, genetic association and clinical trials studies provide considerable evidence for the involvement of the human ¦Ã-aminobutyric acid (GABA) system in the neurobiology of nicotine addiction. However there are few human GABA neurochemical imaging studies of nicotine addiction. We investigated limbic GABA_A receptor availability in volunteers with a history of cigarette smoking using [¹¹C]Ro15 4513 positron emission tomography (PET). Eight [¹¹C]Ro15 4513 PET scans from volunteers with a history of cigarette smoking were compared to twelve scans from volunteers who were non-smokers. Total, ¦Á1 and ¦Á5 GABA_A receptor subtype [¹¹C]Ro15 4513 V_T values were quantified using spectral analysis of limbic regions implicated in nicotine addiction. Spectral analysis allows quantification of the overall [¹¹C]Ro15 4513 spectral frequency as well as ¦Á1 and ¦Á5 GABA_A receptor subtype specific spectral frequency components. Volunteers with a history of cigarette smoking showed significantly higher total [¹¹C]Ro15 4513 V_T values in the presubgenual cingulate and parahippocampal gyrus, and at a trend level in the insula, nucleus accumbens and subgenual cingulate. In six abstinent previous smokers (¡®ex-smokers¡¯), total [¹¹C]Ro15 4513 binding was significantly higher in all limbic regions studied, with higher ¦Á5 availability in the amygdala, anterior cingulate, nucleus accumbens and presubgenual cingulate. These results suggest that limbic GABA_A receptor availability is higher in volunteers with a history of cigarette smoking which may reflect either higher expression of GABA_A receptors or lower endogenous GABA levels. The findings in ex-smokers suggest that higher GABA_A receptor availability continues with abstinence indicating that this may be a trait marker for nicotine addiction or that alterations in GABA function associated with cigarette smoking persist.