The aim of this study was to evaluate the effects of orexin type-1 receptor (OX1R) antagonism in locuscoeruleus (LC) nucleus on the development of morphine physical dependence in rats. Animals were ren-dered 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 admin-istration, the animals received intra-LC administration of SB-334867 (3 mM, 0.2 l), a selective orexintype-1 receptor antagonist. On day 8, naloxone (3 mg/kg, i.p.) was injected and physical dependence wasevaluated for 30 min. Our results showed that administration of OX1R antagonist before each morphineinjection significantly decreased somatic signs of naloxone-induced morphine withdrawal syndrome,including defecation, wet-dog shake, diarrhea, jumping, scratching, and teeth chattering. These resultssuggest that the activation of OX1R in LC nucleus might be involved in the development of morphinedependency.
کلید واژگان :Locus coeruleus, Morphine, SB-334867, Orexin type-1 receptor, Morphine withdrawal syndrome, Rat
ارزش ریالی : 600000 ریال
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