al., 2009; Matsuzawa et al., 1999), whereas studies with a longer pretreatment time (90 minutes) report potentiation of ethanol CPP (Sperling et al., 2010). Interestingly, U50,488 alone elicited a significant conditioned place aversion when administered 15 minutes prior to conditioning trials, with no aversion observed when the agonist was given 30 or 60 minutes prior to conditioning trials (McLaughlin et al., 2006). The importance of timing of U50,488 administration is also observed in studies involving the conditioned rewarding effects of other drugs. For example, multiple reports have shown that U50,488 given 60 minutes before cocaine administration potentiates CPP whereas a 15-minute pretreatment time results in place aversion (McLaughlin et al., 2006; Ehrich et al., 2014). Differential effects of timing of KOR agonist administration on cocaine-induced dopamine release in the nucleus accumbens have also been reported (Ehrich et al., 2014; Chartoff et al., 2016), an effect that has not yet been examined within the context of ethanol-induced dopamine release.
