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 al., 2007) suggesting that EC release may be facilitated. If this results in enhanced EC tone, then CB1 expression would be predicted to decrease as this receptor is rapidly internalized and targeted for lysosomal degradation in response to agonist binding (Martini et al., 2007; Tappe-Theodor et al., 2007). As a consequence, we hypothesize that CB1 expression is likely to be reduced in the midbrain during the initial phase of withdrawal.
