The effects of ethanol in the VTA are more complex than the effects of nicotine. Ethanol, unlike nicotine, is not a direct agonist at nAChRs (Cardoso et al., 1999; Zuo et al., 2002) but can modulate DA release by influencing the function of nAChRs in both the VTA and NAc (Ericson et al., 1998, 2003; Larsson et al., 2005). While local perfusion of ethanol into the VTA does not increase DA release in the accumbens, infusion of ethanol into the accumbens does elevate extracellular DA to a similar degree as systemic administration (Ericson et al., 2003; Tuomainen et al., 2003). However, ethanol infused into both regions simultaneously resulted in higher DA levels than when injected into the NAc alone (Lof et al., 2007). Furthermore, perfusion of mecamylamine (MEC, non-selective nAChR antagonist) into the VTA, but not into the NAc, blocks DA release stimulated by systemic administration of ethanol. It has been postulated that ethanol's actions in the NAc may facilitate the release of endogenous ACh in the VTA, leading to activation of nAChRs and consequently elevating accumbal DA release (Larsson
