Structures within the extended amygdala circuitry that are intimately involved in mediating negative emotional and motivational states associated with stress and chronic alcohol exposure/withdrawal (e.g., CeA, BNST) are rich in DYN and KORs (Mansour et al., 1994; Marchant et al., 2007; Poulin et al., 2009). There is evidence that stress and chronic alcohol exposure increase DYN/KOR function in the CeA and BNST (Chung et al., 2014; Kissler et al., 2014). A number of studies have shown that this upregulation in DYN/KOR signaling contributes to escalated alcohol intake associated with dependence. For example, systemic administration of the KOR antagonist nor-binaltorphimine reduced escalated drinking in dependent rats while not altering more modest intake in nondependent rats (Kissler et al., 2014; Walker and Koob, 2008; Walker et al., 2011). Similar results were reported in mice (Rose et al., 2015). Pharmacological blockade of KORs by direct injection of a KOR antagonist into the CeA (Kissler et al., 2014) or into the nucleus accumbens (Nealey et al., 2011) also was shown to attenuate elevated alcohol consumption in dependent rats. Additionally, systemic administration of the novel
