Effects of KOR activation and blockade on ethanol consumption also appear to be influenced by stress conditions. When mice were repeatedly subjected to social interactions in which they were identified as defeated or victorious, defeated mice consumed more ethanol and showed a further increase when treated with the KOR agonist U50,488 (Kudryavtseva et al., 2006). In another study, mice with a history of stress and ethanol dependence were more sensitive to the effects of KOR blockade on ethanol intake. That is, a short-acting KOR antagonist blocked stress-induced enhancement of ethanol consumption observed in dependent mice but did not alter intake in non-dependent mice (Anderson et al., 2016). These results generally align with studies involving use of transgenic mice. That is, whereas prodynorphin knockout mice consumed a similar amount of ethanol as their wildtype littermates (two-bottle choice drinking in the home-cage), the prodynorphin-deficient mice did not exhibit stress-enhanced drinking observed in wildtype mice (Sperling et al., 2010). In another study, prodynorphin-deficient male and female mice consumed more ethanol compared to their wildtype littermates in a home-cage free-choice drinking paradigm, but the
