Endocrine Abstracts (2006) 11 OC26

Neuropeptide S is a novel peptide which potently stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake

KL Smith, M Patterson, WS Dhillo, SR Patel, NM Semjonous, JV Gardiner, MA Ghatei & SR Bloom


Department of Metabolic Medicine, Imperial College London, London, United Kingdom.


Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the modulation of arousal and fear responses. It has also been shown that lateral ventricle administration of NPS causes a significant decrease in food intake. Neuropeptides involved in the modulation of arousal have been shown to be involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and food intake.

Objective: To examine the effect of NPS on the regulation of the HPA axis, behaviour and food intake.

Methods: ICV cannulated unanaesthetised male rats were injected with NPS and the effects on behaviour and the HPA axis were examined. We then studied the effect of paraventricular nucleus (PVN) administration of NPS on the regulation of the HPA axis, food intake and behaviour. We also examined the effect of NPS on the release of CRH and AVP from hypothalamic explants.

Results: ICV administration of NPS significantly increased plasma ACTH and corticosterone 10 and 40 minutes post injection respectively. A single ICV injection of NPS caused a significant increase in rearing activity as well as ambulatory movement for up to 45 minutes post injection. There was a significant increase in plasma ACTH and corticosterone following a single NPS PVN injection. Incubation of hypothalamic explants with increasing concentrations of NPS caused a significant increase in CRH and AVP release. In addition, PVN administration of NPS dose-dependently inhibited food intake in the first hour post-injection although no effect on food intake was seen after this time point. PVN administration of NPS caused a significant increase in rearing activity.

Conclusion: This data demonstrates that NPS potently stimulates the HPA axis and dose dependently inhibits food intake following PVN administration.

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