The Roles Of NPS On Memory, Colonic Transit And Feeding

Neuropeptide S (NPS) is a recently discovered peptide shown to be involved inregulating arousal and anxiety. NPS receptor (NPSR) mRNA is expressedsignificantly in the major input and output regions of hippocampal formation whichare critical in the modulation of learning and memory. However, the role ofNPS-NPSR system in regulating learning and memory is still unknown. Here, we usethe Morris water maze (MWM) to determine the effects of NPS on spatial learningand memory following intracerebroventricular (i.c.v.) injection in mice. Our datashow that i.c.v, injection of NPS facilitates spatial memory in the MWM withoutsignificant alteration of latency to the target and swimming speed. Furthermore, NPS(i.c.v.) mitigates spatial memory impairment induced by the selectiveN-methyl-D-aspartate receptor antagonist MK801. Taken together, our results firstlydemonstrate that NPS facilitates spatial memory and mitigates MKS01-inducedspatial memory impairment in mice, which implicate that NPS-NPSR system mightbe a new target for enhancing memory and treatment memory impairment.In addition, high levels of NPSR mRNA was detected in various nuclei in thehypothalamus, which is the predominant brain center regulating energy homeostasis.Although it has been reported the feeding regulatory role of NPS in rats and chickens,the results were controversial. Therefore, we investigated the role of NPS-NPSRsystem in food intake in mice. I.c.v. injection of NPS (1-1000 pmol) inhibited foodintake in a dose-dependent manner in fasted mice. Furthermore, i.c.v. co-administration of [D-Val~5]NPS, a pure and potent NPSR antagonist, antagonizedthe inhibitory effects of NPS on food intake. These results firstly inicated that centralinjection of NPS inhibited food intake via central NPSR receptor in mice.NPSR mRNA is expressed in several regions of central autonomic network throughwhich the brain controls visceromotor and other responses essential for survival.Furthermore, many agents, regulating food intake, also regulated gastrointestinalmotility. However, the role of NPS/NPSR system in regulating gastrointestinal motoris still unknown. Therefore,we investigated the role of NPS on gastrointestinalmotility. I.c.v. injection of NPS (1-1000 pmol) did not affect gastric emptying andgastrointestinal transit in mice. However, i.c.v, injection of NPS (1-1000 pmol)inhibited distal colonic transit in a dose-dependent manner. Furthermore, i.c.v.co-administration of [D-Val~5]NPS, a pure and potent NPSR antagonist,dose-dependently antagonized the inhibitory effects of NPS on distal colonic transit.In conclusion, our results firstly indicate that central NPS inhibits distal colonic transitthrough the activation of central NPSR, but, central NPS did not affect gastricemptying and gastrointestinal transit. Our results implicate that NPS-NPSR systemmight be a new target to treat function disorder of distal colon.