title: Antagonism of orexin type 1 receptors in the locus coeruleus attenuates signs of naloxone-precipitated morphine withdrawal in rats.
abstract: It has been shown that orexin neuropeptides contribute to morphine-induced physical dependence. The locus coeruleus (LC), which receives a dense extra-hypothalamic orexinergic projection, is a key brain region implicated in the expression of somatic signs of morphine withdrawal syndrome. The aim of the present study is to investigate the role of LC orexin type 1 receptors (OXR1) on naloxone-precipitated morphine withdrawal signs in rats. Adult male Wistar rats were rendered dependent on morphine by subcutaneous (s.c.) injection of morphine sulfate (10mg/kg) at an interval of 12h for 9 days. On day 10, naloxone (1mg/kg i.p.) was injected 2h after morphine administration. Somatic signs of withdrawal were then evaluated in a clear Plexiglas test chamber (30 cm diameter, 50 cm height) for 25 min. One group of animals received intra-LC SB-334867-A, a selective OXR1 antagonist, (100 microM, 0.2 microl) immediately before naloxone. In the control group, SB-334867-A vehicle was microinjected into the LC in the same manner. The results showed that intra-LC OXR1 receptor blockade significantly decreased the somatic signs of withdrawal including chewing, diarrhea, scratching, teeth chattering, wet-dog shake and ptosis. These results suggest that activation of OXR1 in the LC might be involved in the expression of withdrawal signs in morphine dependent rats.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, IR, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Azizi
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
authors.forename: Kambiz
authors.initials: K
authors.lastname: Rohampour
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009287:Naphthyridines; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D064446:Orexin Receptors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D009292:Narcotic Antagonists; D009294:Narcotics; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D009270:Naloxone; D009020:Morphine; D014508:Urea