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J Neurosci. 2006 Aug 23;26(34):8707-14.

Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers.

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Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA.


Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing beta2-subunits (beta2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of beta2*-nAChRs during early abstinence contribute to the perpetuation of addiction to tobacco smoking. Using molecular imaging, specifically single-photon emission computed tomography with the nAChR agonist radiotracer [123I]5-IA-85380 ([123I]5-IA), we imaged beta2*-nAChR availability in human smokers. First, using nonhuman primates treated chronically with nicotine, we estimated the time interval necessary for smokers to abstain from smoking so that residual nicotine would not interfere with [123I]5-IA binding to the beta2*-nAChR as approximately 7 d. Thus, we imaged human smokers at 6.8 +/- 1.9 d (mean +/- SD) of abstinence. Abstinence was confirmed by daily assessments of urinary cotinine and expired carbon monoxide levels. In smokers, [123I]5-IA uptake was significantly higher throughout the cerebral cortex (26-36%) and in the striatum (27%) than in nonsmokers, suggesting higher beta2*-nAChR in recently abstinent smokers. Beta2*-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke. Higher brain beta2*-nAChR during early abstinence indicates that, when smokers quit smoking, they do so in the face of a significant increase in the receptors normally activated by nicotine. Greater beta2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence.

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