Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders

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.

Keywords: NPS receptor 1 (NPSR1); addiction; behaviour; emotion; neuropeptide S (NPS); rodent; single nucleotide polymorphism; stress.

Figure 1

Overview of the impact of the administration of NPS in various brain areas in rodents. As depicted on this rodent brain (in dark red), the Nps precursor mRNA is expressed discretely in a few brain areas, including the trigeminal sensory nucleus (TSN), the locus coeruleus area (LC), the Kölliker–Füse nucleus of the lateral parabrachial area (KF), the hypothalamus (HYP) and the amygdala (AMY). By contrast to the Nps precursor mRNA, the Npsr1 mRNA is widely expressed in the rodent brain, here shown in the AMY, the bed nucleus of stria terminalis (BNST), the hippocampus (HC), the HYP, the perifornical area (PeF), the nucleus accumbens (NAc) and the ventral tegmental area (VTA). Rodent models allow experimental investigation into the role of the NPS/NPSR1 system in addiction-like and emotional behaviours, as well as neuroendocrine and behavioural stress responsiveness. In the papers analysed in the present review (see summary in Tables 1 and 3), NPS was administered in various brain areas and the effects of NPS were observed at the behavioural, endocrine and molecular level in naïve animals. Similar effects of NPS were generally shown in rodents exposed to stress or with innate pathological phenotypes (here referred to as “animal models”), but other behaviours were affected and highlighted here. Abbreviations: ACTH, adrenocorticotropic hormone; ADR, adrenal; ASR, acoustic startle response; AVP, arginine vasopressin; CPP, conditioned place preference; CORT, corticosterone; CRH, corticotropin-releasing hormone; EXT, extinction; i.c.v., intracerebroventricular; NPSR1, neuropeptide S receptor 1; PIT, pituitary; SA; self-administration; RST, reinstatement. Symbols: ↑, increase; ↓, decrease; ↔, no significant change.