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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Blockade of orexin receptor 1 attenuates the development of morphine tolerance and physical dependence in rats
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Blockade of orexin receptor 1 attenuates the development of morphine tolerance and physical dependence in rats

机译：抑制orexin受体1减弱了大鼠吗啡耐受性和身体依赖性

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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.
机译：这项研究的目的是评估orexin受体1拮抗剂预处理对大鼠吗啡耐受性发展和身体依赖性的影响。通过皮下（SC）注射硫酸吗啡（10 mg / kg），以设定的间隔12小时10天，使动物依赖于吗啡。在服用吗啡之前，这些动物接受了SB-334867，一种选择性的orexin受体1（OXR1）拮抗剂。为了评估对吗啡的耐受性，在给药之前和之后使用温水尾部浸入试验测量了吗啡的镇痛反应。在第11天，吗啡给药后2小时注射纳洛酮，并通过定量/计分纳洛酮沉淀的戒断症状30分钟来评估身体依赖性。慢性SB-334867对运动的影响是通过计算跨网次数来衡量运动活动来进行的。我们的研究结果表明，尽管对吗啡的反复注射会产生吗啡耐受性，但OXR1拮抗剂的预处理阻止了该作用，从而导致了吗啡耐受性的发展延迟。此外，将Orexin受体1拮抗剂与吗啡并用可显着降低戒断的体征，包括腹泻，牙齿颤抖，跳动和排便。单独施用SB-334867或与吗啡长期共同施用均不能改变运动活性。这些结果表明OXR1的激活可能参与吗啡耐受性和依赖性的发展。

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