An intriguing example that has been the subject of recent study is the small-conductance Ca2+-dependent K+ (SK) channel. Ethanol inhibits SK2 channel currents in a heterologous expression system (Dreixler et al., 2000), but there is no evidence of direct ethanol interactions with this channel. However, a number of studies indicate that chronic ethanol exposure and withdrawal reduce SK channel function in the ventral tegmental area (VTA) dopamine, hippocampal CA1 (Figure 3A), and cortical neurons (reviewed in Mulholland et al., 2009, 2011; Nimitvilai et al., 2016a; Korkotian et al., 2013). Furthermore, decreased SK channel expression and function were observed in the nucleus accumbens (NAc) core after ethanol self-administration. This effect was associated with greater ethanol seeking and was blocked by administration of an SK channel activator into the NAc after abstinence (Hopf et al., 2010). Similarly, NAc SK channel inhibition increases ethanol intake in mice (Padula et al., 2015), supporting the association between SK channels and ethanol intake (Figure 3B). Clearly, the SK channel has important roles in neuroadaptations that alter ethanol-related behaviors.
