crucial element of the reward and addiction pathway) are potentiated by alcohol, and this potentiation shows no tolerance throughout the recording session (Figure 4b, αβ4 BK). By contrast, when the β4 auxiliary subunit is absent, alcohol-mediated potentiation of BK channel activity dissipates within 5 min of alcohol exposure (Figure 4b, α BK). In several brain regions, BK channels regulate neuronal excitability by shaping action potential patterns. In the striatum, potentiation of BK channels by alcohol strongly depresses neuronal excitability. This effect persisted for 14 min of recording in αβ4-expressing MSNs (Figure 4c, WT). In contrast, BK channel activity quickly returned to baseline levels in β4 KO mice (Figure 4c, β4 KO), indicating that BK channel-mediated tolerance at the molecular level can also be observed at the cellular level. In mice lacking the β4 subunit, locomotor activity returned rapidly (within a few minutes) to control level following an initial depression, indicating the presence of behavioral tolerance. Finally, and most interesting, these mice drank markedly more than their wild type counterparts (Figure 4d, BK β4 KO). There was no difference found in baseline fluid (water and sucrose) intake in WT and KO mice. These studies underline the concept that alcohol consumption can
