title: Orexin A activates locus coeruleus cell firing and increases arousal in the rat.
abstract: The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an important role in orchestrating the sleep-wake cycle.
authors.affiliation: Neuroscience Research, Europe, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex, United Kingdom CM19 5AW. Jim_Hagan1@sbphrd.com
authors.forename: J J
authors.initials: JJ
authors.lastname: Hagan
authors.forename: R A
authors.initials: RA
authors.lastname: Leslie
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: T A
authors.initials: TA
authors.lastname: Wattam
authors.forename: S
authors.initials: S
authors.lastname: Holmes
authors.forename: C D
authors.initials: CD
authors.lastname: Benham
authors.forename: S G
authors.initials: SG
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Routledge
authors.forename: P
authors.initials: P
authors.lastname: Hemmati
authors.forename: R P
authors.initials: RP
authors.lastname: Munton
authors.forename: T E
authors.initials: TE
authors.lastname: Ashmeade
authors.forename: A S
authors.initials: AS
authors.lastname: Shah
authors.forename: J P
authors.initials: JP
authors.lastname: Hatcher
authors.forename: P D
authors.initials: PD
authors.lastname: Hatcher
authors.forename: D N
authors.initials: DN
authors.lastname: Jones
authors.forename: M I
authors.initials: MI
authors.lastname: Smith
authors.forename: D C
authors.initials: DC
authors.lastname: Piper
authors.forename: A J
authors.initials: AJ
authors.lastname: Hunter
authors.forename: R A
authors.initials: RA
authors.lastname: Porter
authors.forename: N
authors.initials: N
authors.lastname: Upton
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004594:Electrophysiology; D013006:Growth Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000068797:Orexins; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011388:Prolactin; D013006:Growth Hormone; D003345:Corticosterone