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

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.