Evaluation of the effect of risperidone and methyl prednisolone on morphine induced tolerance in mice

Abstract

Introduction: Chronic use of opioid painkillers causes tolerance to the analgesic effect. Increased expression of P-glycoprotein gene in blood-brain barrier causes tolerance. Risperidone inhibits P-glp. Antioxidants are effective in reducing tolerance to morphine;methyl prednisolone and risperidine are antioxidant.Aim: The aim of the present study was to evaluate the effects of chronic intraperitoneal administration of methyl prednisolone and risperidine on the incidence of morphine analgesic tolerance in male mice.Method: 81 male mice in 9 groups of 9 in the weight range of 20-30 grams were randomly selected and received drug regimens containing risperidine and methyl prednisolone once a day for two weeks. Doses of risperidine (0.01,0.02,0.04mg/kg, ip) and methyl prednisolone (10, 20, 40 mg/kg, ip) were injected every half hour before the daily injection of morphine. Then, on the 15th day, the analgesic effects of morphine dose test (9 mg/kg, ip) were evaluated by hot plate method. After conducting behavioral studies in different groups, the animals are anesthetized and blood is taken from the heart to measure the serum level of MDA and TAC.Result: The results showed a significant effect in different doses of methyl prednisolone in reducing tolerance due to morphine injection,and there were significant changes in the serum levels of MDA in 20, 40 mg/kg ,but there were no significant changes in the serum levels of TCA in any of the groups. The selected dose range of risperidone did not have any significant change in reducing tolerance and changes in serum levels.Conclusion: Different doses of methylprednisolone drug were effective in preventing tolerance, and part of this effect may be related to the antioxidant effects of the drug. Also, Risperidone was not able to prevent tolerance in this dose range and it is necessary to study other doses of this drug