1 Department of Clinical Medicine - Translational Neuropsychiatry Unit, Department of Clinical Medicine, Health, Aarhus University2 unknown3 Centre for Psychiatric Research, Faculty of Health Sciences, Aarhus University, Aarhus University4 Department of Clinical Medicine - Translational Neuropsychiatry Unit, Department of Clinical Medicine, Health, Aarhus University
Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion of cannula, 0.25 or 1.0 nmol NPS, or vehicle/5 ml were infused into the lateral ventricle. 45 min after NPS infusion animals were tested on elevated plus maze (EPM). Five days later the animals were subjected to the two-day forced swim test (FST); NPS or vehicle were injected 45 min before the second day FST. In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient findings were: (1) NPS increased in a dosedependent fashion the percent time spent in the open arms and the number of full entries in the FSL rat (p'so0.01), while the effects in the FRL were only marginal; (2) In contrast to altered behavior in the EPM, behavior in the FST was not affected by NPS; (3) In the home cage, NPS increased locomotion in a dose dependent fashion in the FSL; (4) rt-qPCR showed that NPSR expression was lower in amygdalae in the FSL; no other region or strain differences were found. Discussion: Baseline depression-like behavior was markedly higher in the FSL compared to FRL rats while no difference in the anxiety-like behavior was observed. These findings confirm the utility of the FSL as a model of depression useful in exploration of neurobiological correlates both of depression and those discriminating between depression and anxiety endophenotypes. NPS had marked anxiolytic effects but did not modify the depression-like behavior. These results clearly separate effects of NPS from those of the classical antidepressants (tricyclics and SSRIs) which are also anxiolytic, and indicate that NPS agonists could be useful as selective anxiolytic drugs.
Neuropsychopharmacology, 2010, Vol 35
neuropeptide S anxiolytic agent messenger RNA antidepressant agent receptor anxiety rat animal model college psychopharmacology amygdaloid nucleus lateral brain ventricle polymerase chain reaction locomotion infusion cannula female forced swim test male brain hippocampus arm agonist strain difference model endophenotype maze test rodent