course of mu antagonist effects (Wettstein and Grouhel, 1996). Finally, a more recent report calls into question the selectivity of nor-BNI by demonstrating efficacy of the drug in mice lacking KOR receptors (Zhou et al., 2015). These characteristics suggest that, when reporting behavioral effects less than 24 hours after systemic administration of nor-BNI or JDtic, it may be important to rule out contributions of activity at mu receptors (see Schank et al., 2012a). Understanding the time course and magnitude of altered KOR activity/signaling produced by these pharmacological agents will be critical in the interpretation of behavioral results. Development of new, short-acting, and more selective KOR antagonists will be useful in clarifying this issue as well.
