Neuropeptide S alters depression- and anxiety-like behaviors in the Flinders Sensitive Line rats, a genetic animal model of depression

Abstract

Accumulated evidence indicates that  dysregulation of the monoaminergic systems is a sufficient but not a necessary cause of depression and that other transmitters play a role. Nevertheless,  (all) clinically used antidepressive drugs affect monoamines. Unfortunately, about 25-30 percent of patients are treatment resistant and 50 percent may be partial responders. Consequently, there is an imperative need to develop more efficient treatments that will target other systems, e.g. neuropeptides. Neuropeptide S (NPS) is a recently discovered peptide, which is synthesized in a few discrete brainstem nuclei but has receptor expression in many brain regions, including the amygdala and hypothalamus. Behavioral studies, mainly performed in mice, have revealed that NPS modulates fear and arousal responses. Therefore, NPS represents such a neuropeptidergic target for affective disorders.

Flinders Sensitive Line rat strain (FSL) versus Flinders Resistant Line (FRL) has been established as a suitable animal model for studying neurochemical and genetic mechanisms underlying depressive disorders. The aim of the present studies was to assess the effect of intracerebral administration (icv) of NPS on depression- and anxiety- related behavior in male FSL and FRL rats. We demonstrated that icv administration of NPS (0.05, 0.25 and 1.0 nmol/5 μl; 45min before test) to FSL rats changed depression-like behavior in  the Porsolt forced swim test (FST) and anxiety-related behavior as assessed on the elevated plus-maze (EPM) in a dose-dependent manner. In contrast, NPS did not alter the behavior of FRL animals.

In conclusion, our results demonstrate that NPS affects both depression and anxiety related parameters, and might be used to develop novel treatments for affective disorders.