β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

Open Access
Publisher Website
Google Scholar
Abstract
A wealth of evidence from postmortem1-3 and preclinical4-7 studies demonstrates smoking- and nicotine-induced elevations in nicotinic acetylcholine receptors (nAChRs) throughout the brain. We previously demonstrated in vivo higher available levels of nAChR containing the β2 subunit (β2*-nAChR) in recently abstinent tobacco smokers compared with individuals who never smoked (nonsmokers).8 Higher β2*-nAChR availability in smokers may be due to a variety of molecular changes, including increased assembly of α4 and β2 subunits in the endoplasmic reticulum,9 increased transport of receptors to the membrane,10 decreased receptor turnover,11 and/or the presence of nicotine-promoting intracellular maturation of the α4β2-nAChR to a high-affinity conformation.12 Higher β2*-nAChR availability is thought to functionally reflect higher numbers of desensitized receptors.13,14 In addition, smoking 1 cigarette led to receptor occupancy of more than 88%,13 suggesting that smokers maintain saturation of β2*-nAChRs during the day. Thus, a chronic tobacco smoker who maintains persistently elevated nicotine levels may experience repeated cycles of nAChR activation and desensitization in the course of each day.14