title: Blockade of orexin type-1 receptors in locus coeruleus nucleus attenuates the development of morphine dependency in rats.
abstract: The aim of this study was to evaluate the effects of orexin type-1 receptor (OX1R) antagonism in locus coeruleus (LC) nucleus on the development of morphine physical dependence in rats. Animals were rendered dependent on morphine by subcutaneous (s.c.) administration of morphine sulfate (6, 16, 26, 36, 46, 56 and 66 mg/kg, 2 ml/kg) at set intervals of 24 h for 7 days. Immediately before each morphine administration, the animals received intra-LC administration of SB-334867 (3 mM, 0.2 μl), a selective orexin type-1 receptor antagonist. On day 8, naloxone (3 mg/kg, i.p.) was injected and physical dependence was evaluated for 30 min. Our results showed that administration of OX1R antagonist before each morphine injection significantly decreased somatic signs of naloxone-induced morphine withdrawal syndrome, including defecation, wet-dog shake, diarrhea, jumping, scratching, and teeth chattering. These results suggest that the activation of OX1R in LC nucleus might be involved in the development of morphine dependency.
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors: Yousof
authors: Y
authors: Mousavi
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors: Hossein
authors: H
authors: Azizi
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors: Javad
authors: J
authors: Mirnajafi-Zadeh
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors: Mohammad
authors: M
authors: Javan
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran. Electronic address: ssemnan@modares.ac.ir.
authors: Saeed
authors: S
authors: Semnanian
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000633:toxicity; D009021:Morphine Dependence / Q000378:metabolism*; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; 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; D064446:Orexin Receptors; D009020:Morphine; D014508:Urea
keywords: Locus coeruleus; Morphine; Morphine withdrawal syndrome; Orexin type-1 receptor; Rat; SB-334867