Activation of NPSR results in an unusual behavioral profile. On one hand, it has been shown that NPS activates arousal and stress-responsive mechanisms (Smith et al., 2006). Accordingly, and similar to CRF and other stress mediators, NPS potently decreases palatable food intake or feeding elicited by partial restriction (Beck et al., 2005; Cifani et al., 2011; Peng et al., 2010; Smith et al., 2006). However, additional studies have shown that NPS also activates the hypothalamic hypocretin/orexin system (Cannella et al., 2009a; Kallupi et al., 2010; Niimi, 2006) and facilitates home-cage food consumption (Niimi, 2006). Unusually, the pro-arousal and pro-stress properties of NPS are combined with potent anxiolytic-like actions (Jungling et al., 2008; Leonard et al., 2008; Rizzi et al., 2008; Vitale et al., 2008). Furthermore, NPS appears to reduce expression of the conditioned fear response and facilitate fear extinction through actions at extrahypothalamic sites, an effect independent from its immediate anxiolytic-like action (Jungling et al., 2008; Meis et al., 2008).
