Molecular Imaging of 7 Nicotinic Acetylcholine Receptors In Vivo: Current Status and Perspectives

Nicotine, named after the French diplomat Jean Nicot who brought the tobacco plant (Nicotiana tabacum) to France, isolated in 1828 as the major pharmacologically active compound in this plant (Posselt & Reimann, 1828), structurally identified between 1890 and 1893 (Pinner, 1893; Pinner & Wolffenstein, 1891), and first synthesized chemically in 1903 (Pictet, 1903), acts on various subtypes of nicotinic acetylcholine receptors (nAChRs) in the brain and in the periphery (Changeux, 2010; Langley, 1906). Besides tobacco, nicotine is found in plants of the nightshade family (solanaceae) such as tomato, potato, peppers and aubergine (eggplant) but also in tea plants (Schep et al., 2009). Accordingly, it is regularly taken up by the great majority of the human population with a mean daily dietary intake of approximately 1.4 μg per day (Siegmund et al., 1999). The alkaloid is readily absorbed by the lung or intestinal tissue, distributed by the blood and transported across the blood-brain barrier (Allen & Lockman, 2003; Oldendorf et al., 1979). When inhaled it takes about seven seconds for nicotine to reach the brain (Rose et al., 2010), where it binds with high affinity to the heteromeric ┙4┚2 and the homomeric ┙7 nAChRs, the two most abundant nAChR populations (Changeux, 2010). In the brain, nAChRs are involved in attention and cognition, locomotion, vigilance control, and rewarding mechanisms (Changeux, 2010; Graef et al., 2011), and they are suggested to play a major role in brain development (Hruska et al., 2009; Ross et al., 2010). Notably, nicotinic receptors, and in particular ┙7 nAChR, are not only expressed on neurons but virtually on all cell types present in the brain including astrocytes (Sharma & Vijayaraghavan, 2001), microglia (De Simone et al., 2005; Suzuki et al., 2006), oligodendrocyte precursor cells (Sharma & Vijayaraghavan, 2002), and endothelial cells (Hawkins et al., 2005). Accordingly, neuronal and non-neuronal expression of ┙7 nAChR has also been found in peripheral organs (Albuquerque et al., 2009; Sharma & Vijayaraghavan, 2002). Molecular imaging in vivo as considered in this review relates exclusively to the use of radiolabelled receptor ligands, although occasionally optical imaging has been used to investigate the cholinergic system (Prakash & Frostig, 2005). Molecular imaging of ┙4┚2 nAChR in vivo has recently been reviewed (Horti et al., 2010; Sabri et al., 2008). Therefore, the current review is focussed on neuroimaging of ┙7 nAChRs.