title: The orexin-1 receptor antagonist SB-334867 attenuates anxiety in rats exposed to cat odor but not the elevated plus maze: an investigation of Trial 1 and Trial 2 effects.
abstract: The orexins are hypothalamic neuropeptides most well known for their roles in regulating feeding and sleeping behaviors. Recent findings suggest that orexin-A may also modulate anxiety, although how and when the orexin system is involved remains unclear. To address this, we investigated the dose-dependent effects of the orexin-1 receptor antagonist SB-334867 in two rodent models of anxiety: the cat odor avoidance model and the elevated plus maze. In both models we tested the effects of SB-334867 when anxiety is novel (Trial 1) and familiar (Trial 2). In the first experiment, Wistar rats were treated with vehicle or SB-334867 (5, 10 or 20mg/kg, i.p.) prior to their first or second exposure to cat odor. During Trial 1, rats treated with 10mg/kg of SB-334867 approached the cat odor stimulus more than vehicle-treated rats. During Trial 2 the effects were more marked, with 10mg/kg of SB-334867 increasing approach times, increasing the number of times rats exited the hide box to engage in exploratory behavior, and decreasing overall hide times. In addition, the 20mg/kg dose decreased general activity during Trial 2. In the second experiment, the effects of SB-334867 (10 and 20mg/kg) were tested in the elevated plus maze. There were no significant differences produced by drug treatment during either Trial 1 or Trial 2. Results suggest that SB-334867 decreases anxiety induced by some, but not all, stressors.
authors.affiliation: Department of Psychology C3A, Macquarie University, NSW 2109, Australia. Electronic address: Lauren.Staples@mq.edu.au.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Staples
authors.affiliation: Department of Psychology C3A, Macquarie University, NSW 2109, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cornish
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009287:Naphthyridines; D009812:Odorants; D000068796:Orexin Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications; D014508:Urea / Q000008:administration & dosage / 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
keywords: Anxiety; Elevated plus maze; Hypocretins; One trial tolerance; Orexins; Predator odor avoidance; SB-334867