RT Journal Article
SR Electronic
T1 Human Tobacco Smokers in Early Abstinence Have Higher Levels of β<sub>2</sub>* Nicotinic Acetylcholine Receptors than Nonsmokers
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8707
OP 8714
DO 10.1523/JNEUROSCI.0546-06.2006
VO 26
IS 34
A1 Julie K. Staley
A1 Suchitra Krishnan-Sarin
A1 Kelly P. Cosgrove
A1 Erica Krantzler
A1 Erin Frohlich
A1 Edward Perry
A1 Joel A. Dubin
A1 Kristina Estok
A1 Eric Brenner
A1 Ronald M. Baldwin
A1 Gilles D. Tamagnan
A1 John P. Seibyl
A1 Peter Jatlow
A1 Marina R. Picciotto
A1 Edythe D. London
A1 Stephanie O'Malley
A1 Christopher H. van Dyck
YR 2006
UL http://www.jneurosci.org/content/26/34/8707.abstract
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.