title: Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist.
abstract: BACKGROUND
  The orexin (Orx)/hypocretin system has been implicated in reward-seeking, especially for highly salient food and drug rewards. We recently demonstrated that signaling at the OxR1 receptor is involved in sucrose reinforcement and reinstatement of sucrose-seeking elicited by sucrose-paired cues in food-restricted rats. Because sucrose reinforcement has both a hedonic and caloric component, it remains unknown what aspect of this reward drives its reinforcing value.
  
  
  OBJECTIVE
  The present study examined the involvement of the Orx system in operant responding for saccharin, a noncaloric, hedonic (sweet) reward, and in cue-induced reinstatement of extinguished saccharin-seeking in ad libitum-fed vs food-restricted male subjects.
  
  
  METHODS
  Male Sprague Dawley rats were fed ad libitum or food-restricted and trained to self-administer saccharin. We determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10-30 mg/kg) on fixed ratio (FR) saccharin self-administration and on cue-induced reinstatement of extinguished saccharin-seeking.
  
  
  RESULTS
  SB decreased responding and number of reinforcers earned during FR responding for saccharin and decreased cue-induced reinstatement of extinguished saccharin-seeking. All of these effects were obtained similarly in food-restricted and ad libitum-fed rats.
  
  
  CONCLUSIONS
  These results indicate that signaling at the OxR1 receptor is involved in saccharin reinforcement and reinstatement of saccharin-seeking elicited by saccharin-paired cues regardless of food restriction. These findings lead us to conclude that the Orx system contributes to the motivational effects of hedonic food rewards, independently of caloric value and homeostatic needs.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Basic Science Building 406, 173 Ashley Avenue, MSC 510, Charleston, SC 29425, USA.
authors.forename: Angie M
authors.initials: AM
authors.lastname: Cason
authors.forename: Gary
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001583:Benzoxazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005508:Food Deprivation; D008297:Male; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage*; D012646:Self Administration; 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; D000068796:Orexin Receptor Antagonists; D014508:Urea; D012439:Saccharin