Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

The effect of metformin on morphine analgesic tolerance and dependence in rats

(2018) The effect of metformin on morphine analgesic tolerance and dependence in rats. Research in Pharmaceutical Sciences. pp. 316-323. ISSN 1735-5362

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Abstract

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.

Item Type: Article
Keywords: Metformin Morphine Physical dependence Tolerance nitric-oxide synthase protein-kinase-c spinal-cord antinociceptive tolerance induced hyperalgesia withdrawal syndrome activation mechanisms expression stress Pharmacology & Pharmacy
Page Range: pp. 316-323
Journal or Publication Title: Research in Pharmaceutical Sciences
Journal Index: ISI
Volume: 13
Number: 4
Identification Number: https://doi.org/10.4103/1735-5362.235158
ISSN: 1735-5362
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4253

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