The Study On The Role Of Hypothalamus In Anxiolytic Effect Of NPS In Mice

Neuropeptide S (NPS), a bioactive peptide, can selectively bind and activate the cognate receptor-NPSR. In the brain, together with its receptor, NPS, as a peptide transmitter, is involved in several physiological functions, such as arousal/sleep, locator activity, feeding, learn and memory, and addiction. So far, it is well known that central NPS can induce anxiolytic-like effect in rats and mice, and because strong expression of NPS receptor (NPSR) is located in hypothalamus, so we hypothesize that those NPSR distributed in hypothalamus may be involved in the anxiolytic-like effects of NPS. Using elevated plus maze and open field paradigm, we investigate whether intra-hypothalamus (arcuate hypothalamic nucleus, Arc) injection of NPS can induce anxiolytic effects in mice. We find that, in the elevated plus maze paradigm, intra-hypothalamus injection of NPS can dose dependently increase time, distance spent in open arms and entry into open arms, and this effect can be blockade by Peripheral administration of selective NPSR antagonist SHA68in advance. Similarly, in open field, NPS also dose dependently increase time, distance spent in the central zone and entry into the central zone, and pretreatment of SHA68can reversed this effects of NPS. In addition, after intracerebroventricularly(i.c.v) administration of NPS, the expression of c-fos is increased in paraventricular nucleus (PVN) and anterior part of arcuate hypothalamic nucleus. These data indicate that hypothalamus is involved in the regulation of NPS on anxiety, and NPS exert its effect through NPSR located in hypothalamus.