The orexin system regulates alcohol-seeking in rats.
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.
Lawrence
Andrew J
AJ
Brain Injury & Repair Group, Howard Florey Institute, University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia. Andrew.Lawrence@hfi.unimelb.edu.au
Cowen
Michael S
MS
Yang
Hong-Ju
HJ
Chen
Feng
F
Oldfield
Brian
B
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
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