title: Orexin receptor type-1 antagonist SB-334867 inhibits the development of morphine analgesic tolerance in rats.
abstract: Herein the effect of orexin receptor type-1 antagonist SB-334867 on the development of tolerance to analgesic effects of morphine was studied in rats. To incite tolerance, morphine sulfate was injected intraperitoneally (i.p., 10mg/kg) once a day for 7 days. The tail flick test was used to evaluate antinociceptive effects of the morphine. A selective OxR1 receptor antagonist, SB-334867, was microinjected (i.c.v.) into the right cerebral ventricle (10 μg/10 μl) immediately before each morphine injection. Repeated morphine application resulted in tolerance to morphine analgesic effects as a decreasing trend during 7 days. Also, repeated administration of SB-334867 (i.c.v.) alone was without significant effect on the nociception as compared to control. Microinjection of SB-334867 prior to each morphine injection inhibited the development of tolerance, so that the analgesic effects of morphine were significantly higher in SB-334867 plus morphine treated rats than that of vehicle plus morphine treated ones on days 4-7. It is concluded that orexin receptor type-1 might be involved in the development of tolerance to morphine analgesic effects.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Islamic Republic of Iran.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Ranjbar-Slamloo
authors.forename: Hossein
authors.initials: H
authors.lastname: Azizi
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Fathollahi
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009287:Naphthyridines; D059225:Nociception / Q000187:drug effects; D064446:Orexin Receptors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D000701:Analgesics, Opioid; D001583:Benzoxazoles; D009287:Naphthyridines; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D009020:Morphine; D014508:Urea