title: The orexin system regulates alcohol-seeking in rats.
abstract: 1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of alcohol-seeking behaviour, and also attenuated alcohol responding under an operant fixed ratio regimen without affecting water responding. 3. The mRNA encoding orexin within the hypothalamus was expressed at a similar density in iP and non-preferring (NP) rats; chronic consumption of ethanol in iP rats did not significantly regulate the density of this expression, but did increase the area of expression within the lateral, but not medial, hypothalamus. 4. These data indicate that while orexin may not be implicated in the development of an alcohol preference, re-exposure of cues previously associated with alcohol availability is sufficient and adequate to activate orexin-containing neurons and drive reinstatement of alcohol-seeking.
authors.affiliation: Brain Injury & Repair Group, Howard Florey Institute, University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia. Andrew.Lawrence@hfi.unimelb.edu.au
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cowen
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Brian
authors.initials: B
authors.lastname: Oldfield
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D009287:Naphthyridines; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D000068797:Orexins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000502:physiology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D014508:Urea