We showed that dynorphin decreased GABA release and opposed ethanol augmentation of GABA release from CeA neurons. It is important to note that endogenous levels of dynorphin are likely lower than exogenously applied concentrations, and endogenous dynorphin effects are likely smaller than those described in this study. Although one might anticipate desensitization of KOR upon superfusion of large concentrations of exogenous dynorphin (Liu-Chen, 2004), the effect of dynorphin did not weaken after up to 25 minutes of application. We conclude that under normal physiological conditions, ethanol effects on GABAergic transmission in CeA are modulated by endogenous dynorphin levels and actions at KOR, certainly in the ex vivo brain slice and likely also in the CeA of the alcohol-drinking organism.
