Evaluation of the Effects of Cetirizine and Hydroalcoholic Extract of Green Tea on Morphine-Induced Tolerance in male mice

Abstract

Introduction:Chronic consumption of opioid analgesics leads to the development of tolerance to their pain-relieving effects. Some of the factors contribute to this tolerance including increased oxidative stress and upregulation of the P-gp gene expression.Cetirizine is an antihistamine that inhibits P-gp.Green tea extract possesses antioxidant and anti-inflammatory properties and also inhibits P-gp.Therefore, it seems that Cetirizine and green tea extract may be effective in mitigating tolerance.Objective:The aim of this study was to investigate the effects of Cetirizine and hydroalcoholic extract of green tea on morphine-induced analgesic tolerance in the male NMRI albino mice.Methods: Male mice(20-30 g, n=100)were randomly divided into 10 groups of 10 in each. They received Saline(10 ml/kg,ip) or Morphine(25mg/kg,ip) daily for 14days to induce morphine tolerance. On the 15th day, the different doses of Cetirizine(5-10-20mg/kg, ip) were administered in the 3-5groups,and hydroalcoholic green tea extract(50-100-200mg/kg,ip) in the 6-8, EXT (50mg/kg, ip) + Cetrizine (5mg/kg, ip) in the group 9 and DMSO 10% w/v in group 10, Cetirizine(10mg/kg,ip) in the group 11, half an hour before injecting the test dose of Morphine(9mg/kg,ip) in all groups.Results: Cetirizine(5-10-20mg/kg,ip) at 30 minutes and Cetirizine (10mg/kg,ip) at 45 and 60minutes have a significant effect on returning tolerance to the analgesic effects of morphine. While the injection of different doses of EXT(50-200 mg/kg, ip) did not show a significant effect in returning the tolerance to the analgesic effects caused by morphine. In the combined injection of two drugs EXT(50 mg/kg, ip) + Cetirizine(5mg/kg, ip) no significant effect was observed in returning tolerance to the analgesic effects of morphine.Conclusion: Different doses of Cetirizine increase the analgesic effects of morphine in morphine-tolerant animals. In order to obtain the exact mechanism, we need additional studies.