Abstract

The neuropeptide S (NPS) and its receptor (NPSR1) have been extensively studied over the last two decades for their roles in locomotion, arousal/wakefulness and anxiety-related and fear-related behaviours in rodents. However, the possible implications of the NPS/NPSR1 system, especially those of the single nucleotide polymorphism (SNP) rs324981, in stress-related disorders and substance abuse in humans remain unclear. This is possibly due to the fact that preclinical and clinical research studies have remained separated, and a comprehensive description of the role of the NPS/NPSR1 system in stress-relevant and reward-relevant endpoints in humans and rodents is lacking. In this review, we describe the role of the NPS/NPSR1 system in emotionality, stress responsiveness and addiction-like behaviour in rodents. We also summarize the alterations in the NPS/NPSR1 system in individuals with stress-related disorders, as well as the impact of the SNP rs324981 on emotion, stress responses and neural activation in healthy individuals. Moreover, we discuss the therapeutic potential and possible caveats of targeting the NPS/NPSR1 system for the treatment of stress-related disorders. The primary goal of this review is to highlight the importance of studying some rodent behavioural readouts modulated by the NPS/NPSR1 system and relevant to stress-related disorders.

Highlights

  • We have provided a comprehensive overview about the current state of knowledge of the role of the neuropeptide S (NPS)/neuropeptide S receptor 1 (NPSR1) system in emotionality, stress responsiveness and addiction-like behaviours in rodents

  • We have described findings on the potential association of the NPS/NPSR1 system with pathophysiological features of stress-related disorders

  • Much remains to be investigated, especially with respect to the cellular and molecular mechanisms by which the NPS/NPSR1 system is associated with stress responses and subsequent stress-related phenotypes relevant to mental health

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Summary

Introduction

The expression of the Nps precursor gene is limited to the trigeminal principal sensory nucleus, the lateral parabrachial nucleus, the peri-locus coeruleus area, the pontine central gray matter and few scattered neurons of the amygdala (AMY) and the hypothalamic dorsomedial nucleus [1,7,8]. The expression of the Nps precursor gene is restricted to the peri-locus coeruleus area and the Kölliker–Fuse nucleus of the lateral parabrachial nucleus area [9,10] (Figure 1). The Nps mRNA expression has only been examined in the pons and was found in the extension of the medial and lateral parabrachial nuclei, in the Kölliker–Fuse nucleus and around the adjacent lateral lemniscus and the pontine central gray matter [8]. EPM, DaLi, MBT [30,36,37,38] FST

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