title: Neuromedin U(2) receptor signaling mediates alteration of sleep-wake architecture in rats.
abstract: Growing evidence indicates that neuromedin U (NmU) neuropeptide system plays an integral role in mediating the stress response through the corticotrophin-releasing factor (CRF) pathways. Stress is often associated with alteration in sleep-wake architecture both in human and laboratory animals. Here, we investigated whether activation of the NmU₂ receptor, a major high affinity receptor for NmU predominantly expressed in the brain, affects sleep behavior in rats. Effects of single (acute) intracebroventricular (icv) infusion of 2.5 nmol of the full agonists porcine NmU8 and rat NmU23 were assessed on sleep-wake architecture in freely moving rats, which were chronically implanted with EEG and EMG electrodes. In addition, repeated once daily administration of NmU8 at 2.5 nmol during 8 consecutive days (sub-chronic) was studied. Acute icv infusion of NmU23 elicited a robust alteration in sleep-wake architecture, namely enhanced wakefulness and suppressed sleep during the first 4h after administration. Acute infusion NmU8 had no effect on spontaneous sleep-wake architecture. However, sub-chronic icv infusion of NmU8 increased the amount of rapid eye movement (REM) sleep and intermediate stage (IS), while decreased light sleep. Additionally, NmU8 increased transitions from sleep states towards wakefulness suggesting a disruption in sleep continuity. The present results show that central-activation of NmU₂ receptor markedly reduced sleep duration and disrupted the mechanisms underlying NREM-REM sleep transitions. Given that sleep-wakefulness cycle is strongly influenced by stress and the role of NmU/NmU₂ receptor signaling in stress response, the disruption in sleep pattern associated with peptides species may support at least some signs of stress.
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, Dept. of Neurosciences, A Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium. aahnaou@prdbe.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; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology; D014851:Wakefulness / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U; D003346:Corticotropin-Releasing Hormone