title: Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.
abstract: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.
authors.affiliation: Centre for Psychiatric Research, Aarhus University, Aarhus, Denmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Beate C
authors.initials: BC
authors.lastname: Finger
authors.affiliation: Centre for Psychiatric Research, Aarhus University, Aarhus, Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Elfving
authors.affiliation: Centre for Psychiatric Research, Aarhus University, Aarhus, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Keller
authors.affiliation: Centre for Psychiatric Research, Aarhus University, Aarhus, Denmark.
authors.forename: Nico
authors.initials: N
authors.lastname: Liebenberg
authors.affiliation: Centre for Psychiatric Research, Aarhus University, Aarhus, Denmark.
authors.forename: Christina W
authors.initials: CW
authors.lastname: Fischer
authors.affiliation: Department of Pharmacology and Toxicology & Centre of Molecular Biosciences Innsbruck, University of Innsbruck, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.affiliation: Department of Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: David A
authors.initials: DA
authors.lastname: Slattery
authors.affiliation: Department of Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000008:administration & dosage*; D009483:Neuropsychological Tests; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000378:metabolism; D012727:Sex Characteristics; D013045:Species Specificity; D013550:Swimming / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; C568280:neuropeptide S receptor, rat; C534458:neuropeptide S, rat