Neuropeptide-S Evoked Arousal with Electroencephalogram Slow-Wave Compensatory Drive in Rats

Abstract

Objectives: Neuropeptide S (NPS) exerts a dual arousal and anxiolytic effect in rodents, which may indicate the potential of a novel class of therapeutic agents in psychiatry. The purpose of this study is to fully describe the nature of electroencephalogram (EEG)-defined waking that mediates these arousal effects. Methods: Effects of the intracerebroventricular infusion of NPS at 2 different doses were characterized over 20 h on sleep-wake architecture and EEG spectral components in rats that were chronically implanted with epidural electrodes for continuous measurement of sleep polygraphic and EEG variables. Results: NPS (1 and 10 nmol) increased active waking (+88 and +87%, respectively), decreased light slow-wave sleep (lSWS) (–84 and –68%, respectively), deep slow-wave sleep (dSWS) (–47 and –33%, respectively) and rapid-eye-movement sleep (–71 and –70%, respectively) during the first 2 h after infusion. The wake-promoting effect of NPS is consistent with a marked lengthening in latency to sleep onset, a decrease in the number of state transitions from wakefulness to lSWS, and a delayed lSWS compensatory response. Interestingly, NPS significantly enhanced waking EEG theta oscillations and slow wave activity during dSWS. Conclusion: The findings suggest that NPS enhanced a consolidated waking associated with a subsequent compensatory EEG slow-wave homeostatic drive rather than rebound sleep duration. The characteristics of NPS-induced waking coupled with enhanced EEG theta oscillations without rebound in sleep are desirable therapeutic features in wake-promoting agents.

Neuronal Expression of the Human Neuropeptide S Receptor NPSR1 Identifies NPS-Induced Calcium Signaling Pathways

“…Since its discovery, the NPS system has been found to modulate behavior in rodents, mediating anxiolytic effects [ 1 , 4 – 8 ], stimulating locomotion [ 1 , 6 , 9 – 11 ], increasing arousal [ 1 , 12 ], and decreasing food intake [ 13 , 14 ]. Human studies have linked the NPS system and single-nucleotide polymorphisms in the NPSR1 gene to diseases like asthma and allergy [ 15 , 16 ], inflammatory bowel disease [ 17 ], rheumatoid arthritis [ 18 ] and panic disorders [ 19 – 22 ].…”

Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons

“…However, NPS did decrease delta and low theta, suggesting that this treatment favors a cortical arousal state, as previously observed following i.c.v. injection 13,53 . Altogether, the present data suggest that NPS injection into the VLPO might induce NREM sleep delayed onset and disruption of NREM sleep episodes, leading to a sleep instability that favors arousal.…”

Neuropeptide S (NPS) and its receptor (NPSR1) in chickens: cloning, tissue expression, and functional analysis

“…Since its discovery, the NPS-NPSR1 system has been reported to have multiple effects in the central nervous system ( CNS ). In rodents, central administration of NPS caused anxiolytic effects ( Xu et al., 2004 ), increased locomotor activity ( Xu et al., 2004 ; Ahnaou and Drinkenburg, 2012 ), enhanced memory ( Okamura et al., 2011 ), and decreased the length of ketamine-induced anesthesia ( Kushikata et al., 2011 ). Moreover, NPS can stimulate hypothalamic-pituitary-adrenal axis activity including stimulation of adrenocorticotropic hormone ( ACTH ) and corticosterone secretion in rats ( Smith et al., 2006 ).…”