Evaluation of the effect of Artemisia marschalliana aerial organs methanolic extract and paroxetine 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.paroxetine inhibits P-glp. Antioxidants are effective in reducing tolerance to morphine; Artemisia marschalliana and paroxetine are antioxidant.Aim: The aim of the present study was to evaluate the effects of chronic intraperitoneal administration of paroxetine and A.m on the incidence of morphine analgesic tolerance in male mice.Method: 90 male mice in 9 groups of 10 in the weight range of 20-30 grams were randomly selected and received drug regimens containing paroxetine and Artemisia marschalliana once a day for two weeks. Doses of paroxetie (3.5, 7, 14 mg/kg, ip) and A.m (100, 200, 400 mg/kg, ip) were injected every half hour before the daily injection of morphine. Then, on the 15th day, the anti-inflammatory substances caused by the morphine dose test (9mg/kg) were evaluated in different groups by the 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 (p <0.05) of 14mg/kg doses of paroxetine and 400 mg/kg doses of A.m in reducing tolerance due to morphine injection for 14-day. There were significant changes in the serum levels of MDA in some of the groups compared to the control group,but There were no significant changes in the serum levels of TCA in any of the groups compared to the control group.Conclusion: Co-injection of the minimum doses of paroxetine and A.m had not a statistically better effect than injection of each of them alone.