PT - JOURNAL ARTICLE AU - Julie K. Staley AU - Suchitra Krishnan-Sarin AU - Kelly P. Cosgrove AU - Erica Krantzler AU - Erin Frohlich AU - Edward Perry AU - Joel A. Dubin AU - Kristina Estok AU - Eric Brenner AU - Ronald M. Baldwin AU - Gilles D. Tamagnan AU - John P. Seibyl AU - Peter Jatlow AU - Marina R. Picciotto AU - Edythe D. London AU - Stephanie O'Malley AU - Christopher H. van Dyck TI - Human Tobacco Smokers in Early Abstinence Have Higher Levels of β<sub>2</sub>* Nicotinic Acetylcholine Receptors than Nonsmokers AID - 10.1523/JNEUROSCI.0546-06.2006 DP - 2006 Aug 23 TA - The Journal of Neuroscience PG - 8707--8714 VI - 26 IP - 34 4099 - http://www.jneurosci.org/content/26/34/8707.short 4100 - http://www.jneurosci.org/content/26/34/8707.full SO - J. Neurosci.2006 Aug 23; 26 AB - Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing β2-subunits (β2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of β2*-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 β2*-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 β2*-nAChR as ∼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 β2*-nAChR in recently abstinent smokers. β2*-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 β2*-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 β2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence.