Studies using genetic models have also reported mixed findings and equivocal evidence for sex differences in home-cage drinking (Table 4). For example, null mutant female, but not male, mice lacking prodynorphin showed reduced ethanol intake compared to wildtype littermates (Blednov et al., 2006). In another study, both male and female prodynorphin knockout mice consumed more ethanol than wildtype controls in a two-bottle choice home-cage drinking paradigm (Racz et al., 2013). A similar outcome was reported in male prodynorphin knockout mice (Femenia and Manzanares, 2012). There is also a report indicating male dynorphin-deficient mice consumed a similar amount of ethanol compared to their wildtype controls (Sperling et al., 2010). It is unclear whether differences in genotype among the prodynorphin knockout animals used in these studies can explain differences in the reported outcomes. Two studies using transgenic mice targeting the KOR have examined voluntary (2-bottle choice) ethanol consumption in the home-cage, with reduced ethanol intake reported in male (Kovacs et al, 2005) and female (Van’t Veer et al., 2016) KOR knockout mice. Interestingly, binge-like ethanol consumption did not differ between KOR null mutant and wildtype female mice (Van’t Veer et al., 2016).
