The most abundant nAChR found in the brain is the high affinity α4β2* receptor (where * indicates that it can combine with other subunits; Picciotto et al. 1995). These receptors have been implicated in modulating the behavioral effects of nicotine in animal models. Pharmacological blockade of α4β2 nAChRs modulates nicotine self-administration and conditioned place aversion (Corrigall et al. 1994; Jackson et al. 2009; Liu et al. 2007). Furthermore, mice lacking the β2 subunit fail to self-administer nicotine (Picciotto et al. 1998; Pons et al. 2008) and do not exhibit nicotine-induced conditioned place preference (Walters et al. 2006). Moreover, use of genetically modified animals has demonstrated that the α4 subunit modulates nicotine-induced hypothermia, reward, sensitization and tolerance (Pons et al. 2008; Tapper et al. 2007; Tapper et al. 2004). These studies provide evidence for the involvement of α4β2* receptors in nicotine behaviors.
