Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Blockade of orexin receptor 1 attenuates the development of morphine tolerance and physical dependence in rats

(2012) Blockade of orexin receptor 1 attenuates the development of morphine tolerance and physical dependence in rats. Pharmacology Biochemistry and Behavior. pp. 212-219. ISSN 0091-3057

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Abstract

The goals of this study were to evaluate the effects of pretreatment by orexin receptor-1 antagonist on the development of morphine tolerance and physical dependence in rat. Animals were rendered dependent on morphine by subcutaneous (SC) injection of morphine sulfate (10 mg/kg) at set intervals of 12 h for 10 days. Just before the morphine administration, the animals received SB-334867, a selective orexin receptor 1 (OXR1) antagonist. To assess morphine tolerance, the antinociceptive responses of morphine were measured using the warm-water tail immersion test before and after its administration. On day 11, naloxone was injected 2 h after morphine administration and the physical dependence evaluated by quantifying/scoring naloxone-precipitated withdrawal signs for 30 min. The effect of chronic SB-334867 on locomotion was carried out by calculating the number of grid crossings as a measure of locomotor activity. Our findings demonstrated that although morphine-tolerance tended to develop in response to repeated injections of morphine, pre-treatment of OXR1 antagonist prevented this effect, causing a delay in the development of morphine-tolerance. Moreover, co-administration of orexin receptor 1 antagonist with morphine significantly decreased the somatic signs of withdrawal including diarrhea, teeth chattering, jumping, and defecation. Administration of SB-334867 alone or in a chronic co-administration with morphine failed to change locomotor activity. These results suggest that the activation of OXR1 might be involved in the development of morphine tolerance and dependence. (C) 2012 Elsevier Inc. All rights reserved.

Item Type: Article
Keywords: Morphine Orexin receptor 1 Tolerance Dependence Withdrawal syndrome Rat opiate withdrawal lateral hypothalamus periaqueductal gray nucleus-accumbens place preference self-stimulation neurons reward involvement activation Behavioral Sciences Neurosciences & Neurology Pharmacology & Pharmacy
Page Range: pp. 212-219
Journal or Publication Title: Pharmacology Biochemistry and Behavior
Journal Index: ISI
Volume: 103
Number: 2
Identification Number: https://doi.org/10.1016/j.pbb.2012.08.010
ISSN: 0091-3057
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4747

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