title: Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity.
abstract: BACKGROUND
  Orexin-A and orexin-B are hypothalamic neuropeptides derived from a 130-amino acid precursor, prepro-orexin, and are potent agonists at both the orexin-1 (OX1) and orexin-2 (OX2) receptors. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and a role in the regulation of sleep-wake function. The in vivo role of orexin-B is not as clear.
  
  
  OBJECTIVE
  To investigate the behavioural, endocrine and neurochemical effects of orexin-B in in-vivo tests. In a number of experiments, these effects were compared with those of orexin-A.
  
  
  METHODS
  Experiments were carried out in male, Sprague-Dawley rats with a guide cannula directed towards the lateral ventricle. The effects of orexin-B (ICV) upon grooming behaviour were compared with those of orexin-A. The effects of orexin-B upon the motor activity response to both novel and familiar environments were assessed in an automated activity monitor. Orexin-B was tested upon startle reactivity and body temperature. Further, plasma hormones and [DOPAC+ HVA]/[DA] and [5-HIAA]/[5-HT] ratios in six brain areas were measured 40 min post-orexin-B or orexin-A.
  
  
  RESULTS
  The clearest behavioural response to orexin-B was increased motor activity in both novel and familiar environments. Orexin-B-induced hyperactivity was blocked by an OX1 receptor antagonist, SB-334867-A, implicating OX1 receptors in this behavioural response. In common with orexin-A, orexin-B reduced plasma prolactin and failed to influence startle reactivity. However, in contrast with orexin-A, orexin-B increased head grooming but failed to cause a robust whole body grooming response or increase plasma corticosterone levels. Further, orexin-B, but not orexin-A, increased plasma TSH and increased hypothalamic and striatal [5-HIAA]/[5-HT] ratios.
  
  
  CONCLUSIONS
  The present study has demonstrated a number of behavioural, neuroendocrine and neurochemical effects of orexin-B that distinguish it from orexin-A. Further, we have demonstrated a role for OX1 receptors in the actions of orexin-B upon motor activity.
authors.affiliation: Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Declan_Jones-1@sbphrd.com
authors.forename: D N
authors.initials: DN
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Gartlon
authors.forename: F
authors.initials: F
authors.lastname: Parker
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: J P
authors.initials: JP
authors.lastname: Hatcher
authors.forename: A
authors.initials: A
authors.lastname: Johns
authors.forename: R A
authors.initials: RA
authors.lastname: Porter
authors.forename: J J
authors.initials: JJ
authors.lastname: Hagan
authors.forename: A J
authors.initials: AJ
authors.lastname: Hunter
authors.forename: N
authors.initials: N
authors.lastname: Upton
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology*; D006120:Grooming / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D009043:Motor Activity / Q000187:drug effects*; D009287:Naphthyridines; D009479:Neuropeptides / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea