The up-regulation of nAChRs varies with subunit composition, cell type and brain region. Amongst the different subtypes of nAChRs, studies have shown the α4β2*, α3β2*, and α6β2* nAChRs can be activated, desensitized and up-regulated by nicotine concentrations (peak levels between 100 and 500 nM) achieved following cigarette smoking in humans (Nguyen et al., 2003; Parker et al., 2004). The α7 and β4-containing nAChRs appear to be less sensitive to nicotine and require higher concentrations (<10 μM) to activate them. The two accessory subunits α5 and β3 appear to inhibit nicotine-induced receptor up-regulation or down-regulation. In this respect, no up-regulation was reported when α5 subunits were associated with α4β2 nAChRs (Mao et al., 2008) and in the striatum, α6-containing receptors without β3 were down-regulated by nicotine while those containing β3 were unaffected (Perry et al., 2007).
