Both ethanol and nicotine stimulate dopamine release in the accumbens by modulating the activity of VTA neurons via nAChRs (Champtiaux et al., 2003). In the presence of physiologically relevant doses of nicotine (100–500 nM) (Nguyen et al., 2003; Parker et al., 2004), nAChRs are briefly activated followed by rapid desensitization, which entails a reversible inactivation of response. Therefore, nicotine's mechanism of action and downstream consequences are attributed to both receptor activation and desensitization (Mansvelder et al., 2002). The propensity of these receptors to desensitize depends largely on the subunit composition of the nAChR assembly. α7 nAChRs have a much lower affinity for nicotine compared to β2-containing nAChRs and are less susceptible to desensitization in the presence of relevant smoking-related concentrations (Mansvelder and McGehee, 2002; Quick and Lester, 2002; Wooltorton et al., 2003).
