Only three studies have employed genetic mouse models to examine the role of DYN/KOR activity in ethanol-conditioned reward and aversion (Table 4). In accordance with the pharmacological antagonism studies described above, male and female prodynorphin knockout mice were shown to express the same degree of ethanol-induced CPP as their wild-type counterparts when tested in an ethanol-free state (Blednov et al., 2006; Nguyen et al., 2012), whereas female prodynorphin knockout mice exhibited greater CPP relative to wildtype controls when tested in the presence of ethanol (i.e., state-dependent CPP) (Nguyen et al., 2012). Another study reported greater ethanol-induced CPP in male prodynorphin knockout mice (Femenia and Manzanares, 2012). However, this study involved ethanol administration via oral gavage immediately prior to conditioning, a procedural variation that may have contributed to the contrasting outcome. A single report of ethanol-induced CTA in prodynorphin knockout mice observed no changes relative to wild-type mice (Blednov et al., 2006). Thus, genetic deletion of the precursor for DYN generally produced results that are congruent with pharmacological blockade of KORs.
