The effect of chrysin on morphine-induced tolerance and dependence and the role of oxidative stress in mice

Background: Tolerance and dependence are the most important side effects of opioid use, especially morphine. It has also been shown that oxidative stress plays an important role in morphine dependence and tolerance. The purpose of this study was to investigate the effect of chrysin on morphine-induced tolerance and dependence and the role of oxidative stress in mice.Methods: At first, the antinociceptive effects of chrysin were investigated to determine the sub-antinociceptive dose of chrysin and its interference with the antinociceptive effect of a single dose of morphine. A dose of 10 mg/kg was administered for nine days to induce morphine tolerance and dependence. Tolerance was evaluated by the hot-plate test and dependence by naloxone-precipitated morphine withdrawal signs. Chrysin was administered in two acute and chronic routes. Furthermore, oxidative stress factors include activity of catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) and the brain levels of malondialdehyde (MDA) and glutathione (GSH) and nitric oxide (NO) in brain mice were measured by kit methods.Results: The results showed that 150 mg/kg chrysin had no analgesic effect. It was also found that repeated doses of chrysin before each dose of morphine for nine days and acute administration of chrysin inhibited morphine tolerance and dependence. Chronic administration of chrysin was also found to be more effective than acute administration in reducing oxidative stress markers.Conclusion: The results of our study showed that the use of chrysin leads to a decrease in morphine dependence and a reduction in withdrawal syndrome signs and oxidative stress.

کلیدواژه ها:

Morphine ، Tolerance ، Dependence ، Oxidative stress ، Chrysin ، Mice