Another possibility is the requirement of active or functioning KOR in order to permit ethanol actions on GABAergic transmission. The dynorphin/KOR system could be part of the cascade of events leading to increased GABA release by ethanol, for example KOR-induced activation of kinase cascades (Bruchas and Chavkin, 2010) or the unlocking of a particular pool of GABA. Intracellular signaling cascades downstream of KOR activation may interact with cascades activated by receptors for Corticotropin-Releasing Factor, a peptide that participates in ethanol actions in CeA, and that is intimately tied to dynorphin/KOR system activity (Bruchas et al., 2010; Heilig and Koob, 2007; Nie et al., 2004). However, ethanol effects on GABAergic transmission were not diminished by subsequent KOR blockade with norBNI, weakening the argument that functional KORs are required for ethanol effects. Further experiments are necessary to elucidate the exact mechanism of this KOR antagonist blockade or prevention of ethanol effects.
