The effect of metformin on morphine analgesic tolerance and dependence in rats.
The effect of metformin on morphine analgesic tolerance and dependence in rats.
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DOI：
10.4103/1735-5362.235158
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发表时间：
2018-08
影响因子：
2.1
通讯作者：
Kaeidi A
中科院分区：
文献类型：
--
作者：
Fatemi I;Amirteimoury M;Shamsizadeh A;Kaeidi A
阿片类药物耐受性和依赖性是一个世界性的公共卫生问题，给社会带来了沉重的负担。本研究旨在探讨二甲双胍（MET）对大鼠吗啡耐受和依赖发生和表达的影响。为了诱导耐受，将硫酸吗啡注射（10 mg/kg，每天两次，s.c.）7天。在检查期间，动物接受二甲双胍（5和50 mg/kg，经口，每日一次），以评估吗啡耐受性和依赖性的发展。为了评价吗啡耐受性和依赖性的表达，在第7天给予单剂量MET（5和50 mg/kg，口服）。采用甩尾实验评价吗啡耐受的诱导作用。为了评价吗啡依赖性，将纳洛酮诱导的跳跃（5 mg/kg，s.c.）被监控。结果表明，与吗啡+生理盐水处理的大鼠相比，50 mg/kg MET联合给药7天显著降低了吗啡镇痛耐受的形成（P < 0.001）。50 mg/kg MET可明显降低纳洛酮注射动物的跳跃次数和发生率（P < 0.01）。值得注意的是，单剂量给予MET并不能阻止对吗啡的镇痛耐受和身体依赖的表达。根据这些结果，可以得出结论，MET减弱大鼠吗啡镇痛耐受和依赖的发展。
Opiate tolerance and dependence is a worldwide public health problem and gives a significant burden to society. The aim of this study was to evaluate the effects of metformin (MET) on development and expression of morphine tolerance and dependence in rats. For induction of tolerance, morphine sulfate was injected (10 mg/kg, twice a day, s.c.) for 7 days. Animals received metformin (5 and 50 mg/kg, orally, daily) during the examination period for assessing the development of morphine tolerance and dependence. In order to evaluate the expression of morphine tolerance and dependence, single doses of MET (5 and 50 mg/kg, orally) were administered on day 7. Tail flick test was performed to assess the induction of morphine tolerance. For evaluation of morphine dependence, naloxone-induced jumping (5 mg/kg, s.c.) was monitored. Our results showed that 7 days coadministration of 50 mg/kg of MET significantly reduced the development of morphine analgesic tolerance versus morphine + saline treated rats (P < 0.001). Treatment with 50 mg/kg MET reduced the incidence and frequency of jumping in naloxone injected animals (P < 0.01). It is notable that single dose administration of MET, did not prevent the expression of analgesic tolerance and physical dependence to morphine. Based on these results, it can be concluded that MET attenuates the development of morphine analgesic tolerance and dependence in rats.