title: Orexin / hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking.
abstract: The orexin/hypocretin system is involved in several addiction-related behaviors. In the present experiments, we examined the involvement of orexin in heroin reinforcement and relapse by administering the orexin 1 receptor antagonist SB-334867 prior to heroin self-administration or prior to cue-induced or heroin-induced reinstatement of extinguished heroin seeking in male Sprague Dawley rats. SB-334867 (30 mg/kg, intraperitoneal) reduced heroin intake during self-administration under fixed ratio-1 and progressive ratio schedules. SB-334867 also attenuated reinstatement of heroin seeking elicited by cues, but not reinstatement elicited by a heroin prime. These results indicate that orexin antagonism reduces heroin self-administration, and they support a role for orexin in cue-triggered drug relapse.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA. smithrac@musc.edu
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Gary
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology / Q000517:prevention & control*; D001583:Benzoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D003932:Heroin / Q000008:administration & dosage*; D008297:Male; D009287:Naphthyridines; D064446:Orexin Receptors; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors* / Q000502:physiology; D012646:Self Administration; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
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; D003932:Heroin; D014508:Urea