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Neuropeptide S is a neuropeptide expressed in the brain, primarily in glutamatergic neurons near the locus coeruleus and in the trigeminal sensory nucleus, as well as in neurons of the lateral parabrachial nucleus in rat brain.1 It is an agonist of the neuropeptide S receptor (NPSR) with an EC50 value of 9.4 nM for the human peptide to induce intracellular calcium mobilization in HEK293 cells expressing the human receptor.2 Neuropeptide S (0.1-1 nmol), administered either intracerebroventricularly or into the paraventricular nucleus (PVN) of the hypothalamus, increases plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats.3 Administration into the PVN also decreases food intake in the hour following doses of 0.1, 0.3, and 1 nmol. Neuropeptide S decreases anxiety-like and fear behaviors in rodents, decreasing defensive burying in rats, increasing the time mice spend in the open arms of the elevated plus maze, and enhancing contextual fear extinction in mice.4,5

1.Xu, Y.-L., Gall, C.M., Jackson, V.R., et al.Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brainJ. Comp. Neurol.500(1)84-102(2007) 2.Xu, Y.-L., Reinscheid, R.K., Huitron-Resendiz, S., et al.Neuropeptide S: A neuropeptide promoting arousal and anxiolytic-like effectsNeuron43(4)487-497(2004) 3.Smith, K.L., Patterson, M.L., Dhillo, W.S., et al.Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intakeEndocrinology147(7)3510-3518(2006) 4.Vitale, G., Filaferro, M., Ruggieri, V., et al.Anxiolytic-like effect of neuropeptide S in the rat defensive buryingPeptides29(12)2286-2291(2008) 5.Jüngling, K., Seidenbecher, T., Sosulina, L., et al.Neuropeptide S-mediated control of fear expression and extinction: Role of intercalated GABAergic neurons in the amygdalaNeuron59(2)298-310(2008)

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