Other studies have also linked NPS activity to cocaine relapse. Using a drug priming procedure, it was found that ICV injection of NPS reinstated extinguished lever pressing for cocaine in mice (Paneda et al., 2009). This effect appeared to be mediated by a downstream activation of central CRF systems, because it was prevented by administration of a CRF1R antagonist and was absent in CRF1R −/− mice. Notably, the anxiolytic-like effect of NPS was preserved in CRF1R −/− mice, suggesting that this NPS property is independent of CRF1Rs (Paneda et al., 2009).