Because stimulation of nAChRs is intimately linked with the effects of smoking, a longstanding and still developing area of research is the labeling of nAChRs using functional brain imaging. Nicotinic acetylcholine receptors are ligand-gated ion channels consisting of α and β subunits (Court et al. 2000; Hogg et al. 2003). Many nAChRs have been identified, with the heteromeric α4β2 being the most common subtype in the brain and the homomeric α7 being the next most common. Postmortem (Benwell et al. 1988; Breese et al. 1997) and laboratory (Yates et al. 1995) studies demonstrate that smokers have widespread upregulation of nAChRs, likely related to desensitization of these receptors from nicotine exposure. Many animal studies also demonstrate upregulation of nAChRs in response to chronic nicotine administration (e.g., Pauly et al. 1996; Shoaib et al. 1997; Zhang et al. 2002). Thus, nAChRs are a natural target for tracer development in the pursuit of a greater understanding of tobacco dependence and other illnesses with abnormal nAChR levels.
