Fatemi Iman, Amirteimoury Morteza, Shamsizadeh Ali, Kaeidi Ayat
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran.
Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran.
Res Pharm Sci. 2018 Aug;13(4):316-323. doi: 10.4103/1735-5362.235158.
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 ( < 0.001). Treatment with 50 mg/kg MET reduced the incidence and frequency of jumping in naloxone injected animals ( < 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.
阿片类药物耐受性和依赖性是一个全球性的公共卫生问题，给社会带来了沉重负担。本研究的目的是评估二甲双胍（MET）对大鼠吗啡耐受性和依赖性的发展及表达的影响。为诱导耐受性，皮下注射硫酸吗啡（10mg/kg，每日两次），持续7天。在评估吗啡耐受性和依赖性发展的检查期间，动物口服二甲双胍（5mg/kg和50mg/kg，每日一次）。为评估吗啡耐受性和依赖性的表达，在第7天给予单次剂量的MET（5mg/kg和50mg/kg，口服）。进行甩尾试验以评估吗啡耐受性的诱导情况。为评估吗啡依赖性，监测纳洛酮诱导的跳跃反应（5mg/kg，皮下注射）。我们的结果显示，与吗啡+生理盐水处理的大鼠相比，50mg/kg的MET连续7天联合给药显著降低了吗啡镇痛耐受性的发展（P<0.001）。50mg/kg的MET处理降低了注射纳洛酮动物的跳跃发生率和频率（P<0.01）。值得注意的是，单次给药的MET并不能阻止对吗啡的镇痛耐受性和身体依赖性的表达。基于这些结果，可以得出结论，MET可减轻大鼠吗啡镇痛耐受性和依赖性的发展。
