title: N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea (SB334867), a hypocretin receptor-1 antagonist, preferentially prevents ethanol seeking: comparison with natural reward seeking.
abstract: Orexins/hypocretins (Orx/Hcrt) are hypothalamic peptides that regulate a wide range of physiological processes and have been shown to be recruited by drugs of abuse. This study was designed to test the effect of the specific Orx/Hcrt receptor-1 (Hcrt-r1) antagonist, N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea (SB334867), on reinstatement elicited by ethanol (EtOH)-associated stimuli versus stimuli associated with a conventional reinforcer [i.e. SuperSac, consisting of 3% glucose and 0.125% saccharin (w/v)]. SB334867 (1-10 mg/kg, i.p.) dose-dependently reduced reinstatement induced by the EtOH- but not SuperSac-associated stimuli. These findings support a differential role of Hcrt-r1 in mediating EtOH seeking versus natural reward seeking.
authors: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Rémi
authors: R
authors: Martin-Fardon
authors: Friedbert
authors: F
authors: Weiss
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009287:Naphthyridines; D009479:Neuropeptides / Q000502:physiology*; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D051381:Rats; D012054:Reinforcement, Psychology; D012201:Reward; D055502:Secondary Prevention; D012646:Self Administration; D013549:Sweetening Agents / Q000008:administration & dosage; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
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; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D013549:Sweetening Agents; D000431:Ethanol; D014508:Urea