title: The orexin₁ receptor antagonist SB-334867 dissociates the motivational properties of alcohol and sucrose in rats.
abstract: A role for orexin A in mediating the primary and conditioned reinforcing effects of alcohol has been established. It is unclear however whether the contribution of orexins to alcohol reward occurs independently of effects on appetite and feeding, and whether orexins regulate the motivation to consume alcohol compared to other rewards. To examine this further here we investigate the effect of the orexin(1) receptor antagonist, SB-334867, on self-administration of alcohol (10% v/v) under both fixed (FR) and progressive ratio (PR) schedules of reinforcement, and whether this differs from the motivation to administer a natural food reward, sucrose (0.2-0.7% w/v) in alcohol preferring (iP) rats. SB-334867 treatment significantly reduced responding for both alcohol and sucrose under a FR3 schedule; however, at the same dose, reduced responding and break point for ethanol, but not sucrose, under a PR schedule. These findings for the first time implicate a role for orexins in the motivation to self-administer alcohol and suggest that this may occur independent of any generalized effect on appetitive drive.
authors: Florey Neuroscience Institutes, Parkville, Victoria 3010, Australia.
authors: Bianca
authors: B
authors: Jupp
authors: Bedrija
authors: B
authors: Krivdic
authors: Elena
authors: E
authors: Krstew
authors: Andrew J
authors: AJ
authors: Lawrence
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001583:Benzoxazoles / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009042:Motivation / Q000187:drug effects*; D009287:Naphthyridines; D064446:Orexin Receptors; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage*; D013997:Time Factors; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D000431:Ethanol; D013395:Sucrose; D014508:Urea