of the ventral tegmental area (VTA), resulting in dopamine release in the nucleus accumbens and contributing to the rewarding and motivational effects of nicotine (Corrigall et al. 1994; Laviolette and van der Kooy 2004; Mineur and Picciotto 2008; Nisell et al. 1994). Further, molecular alterations in central dopamine systems contribute to craving and modulate the aversive effects of nicotine withdrawal (Changeux 2010; Laviolette and van der Kooy 2004; Mansvelder et al. 2002; Mansvelder and McGehee 2002). While a single cigarette smoked in the morning can saturate and desensitize roughly 80–90% of nAChRs for several hours, smokers may continue to smoke throughout the day to avoid having free unbound receptors (Brody et al. 2006). The free, non-desensitized receptors may be responsible for cravings and continued smoking acts on these receptors to provide positive reinforcement and sustained dopamine release to prevent withdrawal symptoms (Balfour 2004; Brody et al. 2006).
