The majority of studies investigating the effects of KOR activation in various rat strains report a decrease in ethanol consumption following systemic or intra-hypothalamic administration of the KOR agonist U50,488. Interestingly, all of the studies conducted in C57BL/6J mice involving KOR agonists report increased ethanol consumption, although one study reported this increase only in mice subjected to social stress (Kudryavtseva et al., 2006). Thus, there is an apparent species difference with regard to effects of a KOR agonist on ethanol consumption in a 2-bottle choice situation. Interestingly, differences in timing of drug administration or duration of access to ethanol do not appear to explain the apparent opposite effects reported in rats and mice.
