The endogenous peptide dynorphin activates kappa opioid receptors (KOR) in the brain (Chavkin et al., 1982), and the dynorphin/KOR system modulates affective-like states (Knoll and Carlezon, Jr., 2010). Several studies suggest that multiple physiological and behavioral effects of ethanol involve KOR (Dar, 1998; Matsuzawa et al., 1999; Pohorecky et al., 1989), and mice lacking KOR exhibit decreased alcohol consumption (Kovacs et al., 2005). Ethanol treatment upregulates dynorphin and its precursor prodynorphin as well as KOR mRNA in the CeA (D’Addario et al., 2011; Lam et al., 2008), and ethanol also increases prodynorphin levels in the nucleus accumbens and prefrontal cortex (D’Addario et al., 2011; Marinelli et al., 2006). Dynorphin peptide and gene expression are activated in the amygdala during acute and chronic administration of alcohol and the KOR antagonist nor-binaltorphimine (norBNI) reduces ethanol self-administration in alcohol-dependent animals (Walker and Koob, 2008). However, little is known about the role of the dynorphin/KOR system in regulating the cellular effects of ethanol.
