These data collectively support a role of NK1R activation in rewarding properties of opioids, and suggest the possibility that NK1R antagonists may be useful for the treatment of opioid addiction through blockade of opioid reward. Surprisingly, however, an initial human laboratory study found that a single administration of the NK1R antagonist aprepitant potentiated, rather than inhibited, subjective as well as physiologic responses to an opioid challenge in prescription opioid abusers (Walsh et al., 2012). A direct assessment of opioid self-administration following NK1R blockade is therefore critical, but has to date not been obtained in laboratory animals or humans. Furthermore, the role of the NK1R in opioid-related behaviors influenced by stress, for example stress-induced reinstatement of opioid seeking after extinction, has not been explored.
