Neurochemical studies have suggested that central injection of NPS facilitates corticomesolimbic DA neurotransmission, a hallmark of reward (Mochizuki et al., 2010; Si et al., 2010). However, ICV NPS administration induced neither place preference nor aversion (Li et al., 2009), suggesting that NPS is devoid of direct rewarding properties. When co-administered with morphine, NPS blocked the acquisition of morphine conditioned place preference (Li et al., 2009), which might suggest that NPS can block reward from drugs of abuse, but central injection of NPS or selective antagonism of the NPSR did not influence cocaine self-administration (Kallupi et al., 2010; Okamura et al., 2008). Genetic influences affect the impact of NPS on alcohol consumption in rats, with alcohol-preferring rat strains exhibiting decreased alcohol drinking in response to NPS (Badia-Elder et al., 2008) (Cannella et al., 2009a; Cannella et al., 2009b). The alcohol-preferring rat strains used in these studies are highly stress-reactive, and show increased measures of anxiety-like behavior. It is therefore possible that, in alcohol preferring rats, NPS decreases alcohol consumption through its anxiolytic-like properties.
