Evaluation of the effectes of atorovastatin and simvastatin on morphine induced tolerance in mice

Abstract

Introduction: Morphine is one of the most widely used opioid analgesic that is used to control severe pain. Tolerance to the analgesic effects of morphine is one of the problems caused by the chronic use of morphine. Several mechanisms (inhibition of NMDA receptors, increased p-gp gene expression, etc.) are involved in the emergence of tolerance to the analgesic effects of morphine. Atorvastatin and simvastatin are both from the family of statins and also they are P-glycoprotein inhibitors.Purpose: The purpose of this study was to investigate the effects of atorvastatin and simvastatin in reducing tolerance to the analgesic effects of morphine in mice. Methods: 80 male mice in 8 groups of 10 in the weight range of 20-30 grams were selected randomly and they received Saline (10 ml/kg, ip) or Morphine (25 mg/kg ip) to develop tolerance to morphine once a day for fourteen days. Then on the fifteenth day, different doses of atorvastatin (5-10-20 mg/kg, ip) in groups 3-5 and simvastatin (2.5-5-10 mg/kg, ip) in groups 6-8 were injected to the mice. The analgesic effects caused by morphine test dose (9mg/kg, ip) were evaluated by hot plate method.Results: The results showed that different doses of atorvastatin (5-10-20mg/kg, ip) did not have a significant effect on reversing tolerance to the analgesic effects caused by morphine. while significant effect of simvastatin (2.5mg/kg, ip) was effective in reversing the tolerance to the analgesic effects of morphine (P<0.01). Conclusion: Simvastatin has beneficial effects in dose of (2.5mg/kg, ip) in reversing tolerance to the analgesic effects of morphine.