Because the DYN/KOR system has been shown to play a role in the regulation of water balance and feeding behavior, it is important to establish selectivity of pharmacological effects for ethanol consumption. Indeed, studies conducted in transgenic mice suggest that genetic deletion of KORs or prodynorphin alters intake of saccharin and sucrose solutions (Kovacs et al., 2005; Blednov et al., 2006). Fortunately, many of the studies in this review included control solutions for comparison. For example, the KOR agonist U50,488 (at doses that reduced operant self-administration of 10% ethanol) also reduced self-administration of 2% sucrose (Henderson-Redmond and Czachowski, 2014). Another KOR agonist, Mesyl Salvinorin B, reduced ethanol intake but did not influence homecage consumption of 4% sucrose or 0.1% saccharin (Zhou et al., 2017). Effects of KOR antagonism are more consistent, with the majority of reports observing no effects of KOR antagonists on intake of sweetened control solutions (e.g., Nestby et al., 1999; Morales et al., 2014; Schank et al., 2012a; Doyon et al., 2006) or water (e.g., Lindholm et al., 2001; Mitchell et al., 2005; Rorick-Kehn et al., 2014) in homecage or operant self-administration procedures.
