Although a large literature provides evidence that stress activates and upregulates the DYN/KOR system and supports a role for DYN/KOR activity in mediating behavioral responses to various stress events (Crowley and Kash, 2015; Knoll and Carlezon, 2010; Van’t Veer and Carlezon, 2013), fewer studies have examined DYN/KOR system involvement in stress-ethanol interactions. In one report, nor-BNI blocked stress-enhanced ethanol CPP in mice exposed to forced swim stress prior to conditioning (Sperling et al., 2010). In contrast, nor-BNI further enhanced ethanol-induced CPP in rats exposed to a stress-associated context (fear) prior to the CPP procedure, an effect that was not examined in non-stressed subjects (Matsuzawa et al., 1999). In yet another account, nor-BNI blocked expression of ethanol-induced CTA in stressed rats, but not their non-stressed counterparts (Anderson et al., 2013). Thus, although stressed animals may be more sensitive to effects of KOR antagonism on ethanol reward, the direction of the reported effects has been inconsistent. Because relatively few studies have addressed this issue, it is difficult to identify experimental factors that might contribute to these discrepant results.
