protein that regulates HPA axis function, is implicated in severity of withdrawal, childhood trauma, aggression and suicidal behavior (Bevilacqua et al., 2012; Huang et al., 2014). Opioid Receptor Kappa 1 subtype (OPRK1), is one of the major subtypes of opioid receptors in the brain particularly localized to limbic brain regions that regulate emotion and reward. Activation of OPRK1 results in behavioral dysphoria during escalated drug or alcohol consumption and withdrawal leading to a negative affective emotional state characterized by increased stress reactivity, irritability, depression, and anhedonia. Negative reinforcement processes that are initiated alleviate the negative affective state of alcohol abstinence/withdrawal, by resumption of hazardous drinking, which perpetuates the addiction cycle. In support of this, a variant in OPRK1 is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk (Faisal et al., 2014; Xu et al., 2013; Xuei et al.,2006). Prodynorphin (PDYN) is a preproprotein that is proteolytically processed to form the secreted opioid peptides beta-endorphin, dynorphin, leu-enkephalin, rimorphin, and leumorphin. These endogenous opioids are ligands for several different subtypes of opioid receptors; the proteolytic product, dynorphin, has been studied most extensively, which binds to the kappa opioid receptor (OPRK1). A recent paper reported an
