Abstract

Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness and arousal with simultaneous anxiety reduction, in some inconsistency with results in humans. We examined the effect of NPS on rat ultrasonic vocalizations (USV) as an index of affective state and on behaviour in novel environments in rats with persistent inter-individual differences in exploratory activity. Adult male Wistar rats were categorised as of high (HE) or low (LE) exploratory activity and NPS was administered intracerebroventricularly (i.c.v.) at a dose of 1.0 nmol/5 µL, after which USVs were recorded in the home-cage and a novel standard housing cage, and behaviour evaluated in exploration/anxiety tests. NPS induced a massive production of long and short 22 kHz USVs in the home cage that continued later in the novel environment; no effect on 50 kHz USVs were found. In LE-rats, the long 22 kHz calls were emitted at lower frequencies and were louder. The effects of NPS on behaviour appeared novelty- and test-dependent. NPS had an anxiolytic-like effect in LE-rats only in the elevated zero-maze, whereas in HE-rats, locomotor activity in the zero-maze and in a novel standard cage was increased. Thus NPS appears as a psychostimulant peptide but with a complex effect on dimensions of affect.

Highlights

  • Neuropeptide S (NPS), a 20 amino acid peptide transmitter, has been at the forefront of neuropsychiatric peptide research since the endogenous ligand for G-protein coupled NPS receptor (NPSR), formerly known as an orphan receptor GPR154, was identified almost20 years ago by Reinscheid and colleagues [1]

  • NPSR is widely distributed, including regions of the hypothalamus, thalamus, cortex, and amygdala [1,2] that are implicated in the regulation of, e.g., homeostasis, sensory gating, and emotional processing

  • NPS has robustly increased locomotor activity in mice and rats both in novel and habituated surroundings and anti-anxiety effects have been reported in a variety of behavioural tests [3,4,5,6,7]

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Summary

Introduction

Neuropeptide S (NPS), a 20 amino acid peptide transmitter, has been at the forefront of neuropsychiatric peptide research since the endogenous ligand for G-protein coupled NPS receptor (NPSR), formerly known as an orphan receptor GPR154, was identified almost20 years ago by Reinscheid and colleagues [1]. Neuropeptide S (NPS), a 20 amino acid peptide transmitter, has been at the forefront of neuropsychiatric peptide research since the endogenous ligand for G-protein coupled NPS receptor (NPSR), formerly known as an orphan receptor GPR154, was identified almost. NPSR is widely distributed, including regions of the hypothalamus, thalamus, cortex, and amygdala [1,2] that are implicated in the regulation of, e.g., homeostasis, sensory gating, and emotional processing. NPS modulates wakefulness, arousal, feeding, memory, and anxiety-like states in rodents. Intracerebroventricular (i.c.v.) administration of NPS elicits a unique behavioural profile of increased wakefulness and arousal along with anxiolytic-like effects at similar doses [1,3]. NPS has robustly increased locomotor activity in mice and rats both in novel and habituated surroundings and anti-anxiety effects have been reported in a variety of behavioural tests [3,4,5,6,7]

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