Because both stress and chronic alcohol engage the DYN/KOR system, the role of this neuropeptide system in alcohol dependence-related stress/dysphoria and elevated drinking has gained increasing attention (Kissler et al., 2014; Wee and Koob, 2010). Dynorphins (DYN) are peptides derived from the precursor prodynorphin (Pdyn) that preferentially bind to kappa opioid receptors (KOR), producing physiological and behavioral effects via inhibitory G-protein (Gi) coupling and other signaling cascades (Bruchas and Chavkin, 2010; Bruchas et al., 2010; Crowley and Kash, 2015; Wee and Koob, 2010). KOR activation has been shown to produce aversive/dysphoric effects as indicated by measures of conditioned avoidance, anxiety-like, and depression-like behavior (Knoll and Carlezon, 2010; Van't Veer and Carlezon, 2013). Stress exposure activates the DYN/KOR system, eliciting dysphoria-like responses, increasing anxietylike behaviors (Land et al., 2008) and resulting in elevated DYN immunoreactivity in brain regions that are integral to reward and stress circuitries involved in alcohol/drug addiction (Shirayama et al., 2004). Further, pharmacological manipulation of KOR activity alters behavioral responses to stress and motivational effects of alcohol. For example, KOR agonists have been shown to produce a state
