at least one study has reported elevated EC content (Mitrirattanakul et al., 2007; Ortiz et al., 2004). Interestingly, two studies that allowed subjects to go through a several week-long withdrawal prior to testing EC content or CB1 expression found elevated levels of both (Mitrirattanakul et al., 2007; Rimondini et al., 2002). These data suggest that EC tone may be persistently increased well into abstinence, and CB1 expression is up-regulated over time to allow the EC system to respond to phasic changes. An important caveat in interpreting these findings is that most of this data pertains to forebrain structures including the hippocampus, cortex, amygdala, striatum and NAc. Data from our lab suggests that sub-chronic treatment with ethanol produces an up-regulation in the expression of CB1 in midbrain (Pava et al., 2012), but to date, no published studies of long-term treatment have examined midbrain CB1 or EC levels. However, EC release at GABAergic synapses onto VTA DA neurons is under control of SK channels, and treatment of these cells with the SK channel blocker, apamin, is known to reduce GABA release via a CB1-dependent mechanism (Riegel and Lupica, 2004). SK channel function is reduced in the VTA following chronic ethanol (Hopf et
