title: Neuropeptide-S evoked arousal with electroencephalogram slow-wave compensatory drive in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Janssen Research and Development, Department of Neurosciences, Johnson and Johnson Pharmaceutical Companies, Beerse, Belgium. aahnaou@its.jnj.com
authors.forename: A
authors.initials: A
authors.lastname: Ahnaou
authors.forename: W H I M
authors.initials: WH
authors.lastname: Drinkenburg
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects*; D058256:Brain Waves / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004328:Drive; D004569:Electroencephalography; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D017286:Polysomnography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D018709:Statistics, Nonparametric; D014851:Wakefulness / Q000187:drug effects
chemical_list: D009479:Neuropeptides; C534458:neuropeptide S, rat