The facilitatory role of NPS on relapse is further supported by experiments using a conditioned reinstatement model of cocaine seeking (Kallupi et al., 2010). In this study, NPS potently reinstated relapse following ICV or intra-lateral hypothalamus microinfusion. Administration of the NPSR antagonist SHA 68 reduced cue-induced reinstatement of cocaine seeking, supporting a role for endogenous NPS in cocaine relapse. In this system, the effect of NPS on drug relapse is mediated by downstream activation of both the hypocretin/orexin and CRF1R systems.
