Intraventricular administration of neuropeptide S has reward-like effects.

Neuropeptide S (NPS) is an endogenous brain peptide produced by neurons located in the lower brainstem, and functional studies suggest that NPS has arousing effects. Because its receptors are found in reward-associated regions throughout the brain, we evaluated whether intraventricular NPS injections elicit reward-related effects in rats. Rats increased lever presses that led to intraventricular administration of NPS (0.34-34 pmol per infusion) in a dose dependent manner, with a cue-assisted procedure. Cue-assisted self-administration of NPS was decreased by systemic administration of the dopamine receptor antagonist SCH 23390 (0.025 mg/kg, i.p.) or the hypocretin-1 (orexin-1) receptor antagonist SB 334867 (20 mg/kg, i.p.). In addition, intraventricular NPS injections (1000 pmol) induced conditioned place preference, whereas a lower dose (100 pmol) of NPS induced conditioned place aversion. Finally, NPS injections (100-1000 pmol) acutely facilitated locomotor activity, whereas repeated NPS injections did not lead to locomotor sensitization. Our data suggest that intraventricular NPS injections have reward-like effects in that NPS weakly facilitates seeking and induces positive reinforcement. These effects may depend on intact dopamine and hypocretin systems.