In contrast to its role in opioid-related behaviors, disruption of NK1R signaling does not affect cocaine conditioned place preference, self-administration, or locomotor sensitization (Gadd et al., 2003; Murtra et al., 2000; Ripley et al., 2002). However, there is some evidence that NK1R antagonists can suppress cocaine-induced locomotion (Kraft et al., 2001) and that relapse to cocaine seeking following extinction can be triggered by ICV infusion of a specific NK1R agonist (Placenza et al., 2005) or intra-VTA infusion of an SP analogue (Placenza et al., 2004). However, an NK1R specific antagonist was unable to prevent reinstatement of cocaine seeking induced by cocaine priming (Placenza et al., 2005). One possibility is therefore that exogenous SP is able to activate pathways involved in reinstatement of cocaine seeking, but this may not reflect actions of endogenous SP. Alternatively, cocaine-induced reinstatement may be mediated by an NK receptor other than NK1R, such as NK3R. Finally, it is possible that the NK1R is involved in reinstatement of cocaine seeking triggered by some stimuli, but not that induced by drug priming. Reinstatement induced by stress is clearly a candidate here, given the role of SP/NK1R in stress responses.
