Blockade of orexin type-1 receptors in locus coeruleus nucleus attenuates the development of morphine dependency in rats

•Orexin has been reported to be involved in morphine physical dependence.•LC is a key brain region implicated in the expression of morphine withdrawal syndrome.•Intra-LC injection of SB-334867 before each morphine injection attenuates morphine dependency. The aim of this study was to evaluate the ef...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience letters 2014-08, Vol.578, p.90-94
Main Authors: Mousavi, Yousof, Azizi, Hossein, Mirnajafi-Zadeh, Javad, Javan, Mohammad, Semnanian, Saeed
Format: Article
Language:English
Subjects:
Animals
Benzoxazoles - pharmacology
Locus coeruleus
Locus Coeruleus - metabolism
Male
Morphine
Morphine - toxicity
Morphine Dependence - metabolism
Morphine withdrawal syndrome
Orexin Receptor Antagonists
Orexin Receptors - metabolism
Orexin type-1 receptor
Rat
Rats
Rats, Wistar
SB-334867
Substance Withdrawal Syndrome - metabolism
Urea - analogs & derivatives
Urea - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Orexin has been reported to be involved in morphine physical dependence.•LC is a key brain region implicated in the expression of morphine withdrawal syndrome.•Intra-LC injection of SB-334867 before each morphine injection attenuates morphine dependency. 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 66mg/kg, 2ml/kg) at set intervals of 24h for 7 days. Immediately before each morphine administration, the animals received intra-LC administration of SB-334867 (3mM, 0.2μl), a selective orexin type-1 receptor antagonist. On day 8, naloxone (3mg/kg, i.p.) was injected and physical dependence was evaluated for 30min. 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.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2014.06.038