title: Neuropeptide S reduces mouse aggressiveness in the resident/intruder test through selective activation of the neuropeptide S receptor.
abstract: Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). In particular NPS evokes robust anxiolytic-like effects in rodents together with a stimulant and arousal promoting action. The aim of the study was to investigate the effects of NPS on the aggressiveness of mice subjected to the resident/intruder test. Moreover the putative role played by the endogenous NPS/NPSR system in regulating mice aggressiveness was investigating using mice lacking the NPSR receptor (NPSR(-/-)) and the NPSR selective antagonists [(t)Bu-D-Gly(5)]NPS and SHA 68. NPS (0.01-1 nmol, icv) reduced, in a dose dependent manner, both the time that resident mice spent attacking the intruder mice and their number of attacks, producing pharmacological effects similar to those elicited by the standard anti-aggressive drug valproate (300 mg/kg, ip). This NPS effect was evident in NPSR wild type (NPSR(+/+)) mice but completely disappeared in NPSR(-/-) mice. Moreover, NPSR(-/-) mice displayed a significantly higher time spent attacking than NPSR(+/+) mice. [(t)Bu-D-Gly(5)]NPS (10 nmol, icv) did not change the behavior of mice in the resident/intruder test but completely counteracted NPS effects. SHA 68 (50 mg/kg, ip) was inactive per se and against NPS. In conclusion, this study demonstrated that NPS produces anti-aggressive effects in mice through the selective activation of NPSR and that the endogenous NPS/NPSR system can exert a role in the control of aggressiveness levels under the present experimental conditions.
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Via Fossato di Mortara 19, 44121 Ferrara, Italy. Electronic address: chiara.ruzza@unife.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruzza
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Laila
authors.initials: L
authors.lastname: Asth
authors.affiliation: Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D023303:Oxazolidinones / Q000494:pharmacology; D010641:Phenotype; D011619:Psychotropic Drugs / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011897:Random Allocation; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: C529493:3-oxo-1,1-diphenyltetrahydrooxazolo(3,4-a)pyrazine-7-carboxylic acid 4-fluorobenzylamide; D002491:Central Nervous System Agents; D009479:Neuropeptides; D023303:Oxazolidinones; D011619:Psychotropic Drugs; D011719:Pyrazines; D018013:Receptors, Neuropeptide; C583532:neuropeptide S receptor, mouse; C539972:neuropeptide S, mouse; D014635:Valproic Acid
keywords: Aggressiveness; Mice; NPSR knockout mice; Neuropeptide S; Neuropeptide S receptor; Resident/intruder test; SHA 68; [(t)Bu-D-Gly(5)]NPS