The role of intracellular signaling pathways in this potentiating EtOH effect has also been examined. It is well established that activation of AC or PKC potentiates transmission at synapses throughout the nervous system (see Leenders and Sheng 2005; Nguyen and Woo 2003 for review). Thus, it is logical to speculate that these signaling molecules might play a role in the acute alcohol action. Potentiation of GABA release onto cerebellar Purkinje neurons is eliminated in the presence of AC and protein kinase A (PKA) inhibitors (Kelm et al. 2008), and is also affected by compounds targeting phospholipase C and PKC (Kelm et al. 2010). The potentiating effect of EtOH is impaired in central amygdala (CeA) in mice that lack PKCε (Bajo et al. 2008). Thus, PKC is implicated in both the pre and postsynaptic effects of EtOH at GABAergic synapses. It is notable that GABA release appears to be increased in the PKCε knockout mice prior to EtOH exposure, and thus the effect in this case may be more akin to occlusion rather than blockade of the drug action. It remains to be determined whether the effects of EtOH on these signaling molecules are direct or indirect.
