title: The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S.
abstract: Neuropeptide S (NPS) is a recently discovered neurotransmitter that binds to its cognate G-protein coupled receptor, NPSR. Previous studies have shown that central administration of this peptide induces anxiolytic-like effects, promotes arousal and inhibits feeding in the same dose range. In the present study, we sought to investigate further the unique physiopharmacological profile of the NPS system by characterizing its effects on palatable food consumption in rats and comparing it with the effect of the classical anxiolytic benzodiazepine midazolam. The results demonstrated that midazolam (5.0 or 10.0 mg/kg) increases palatable food consumption, while intracerebroventricular (ICV) administration of NPS markedly reduces it. The anorectic effect of NPS (0.1-1.0 nmol per rat, ICV) was prevented by ICV pretreatment with the NPSR antagonist [D-Cys(tBU)(5)]NPS (20.0-60.0 nmol per rat). Pretreatment with the nonselective corticotrophin-releasing factor receptor (CRF) antagonist alpha-helical CRF 9-41 (6.25 and 12.5 nmol per rat) completely reversed the hypophagic action of CRF (0.4 nmol per rat, ICV) but did not prevent the anorectic effect of ICV NPS (1.0 nmol per rat). Brain site-specific microinjection experiments revealed that NPS markedly inhibits palatable food intake if administered into the paraventricular nucleus of the hypothalamus (PVN). A similar but smaller and shorter lasting reduction of feeding was observed following intra-lateral hypothalamus administration, whereas no effect was observed following injection into the central amygdala. The present study demonstrates that NPS evokes a potent inhibition of palatable food consumption and that the PVN is an important site of action for its effect.
authors.affiliation: Department of Experimental Medicine and Public Heath, University of Camerino, 62032, Camerino, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Fedeli
authors.forename: Simone
authors.initials: S
authors.lastname: Braconi
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Cannella
authors.forename: Marsida
authors.initials: M
authors.lastname: Kallupi
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D018757:GABA Modulators / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018757:GABA Modulators; D006727:Hormone Antagonists; D009479:Neuropeptides; D010446:Peptide Fragments; C535232:neuropeptide S, 5-Cys(tBu)-; C534458:neuropeptide S, rat; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D008874:Midazolam