Evaluation the effects of chronic administration of methanolic extract of rhizome of Marrubium parviflorum on the development of tolerance to morphine analgesia in male rats

Abstract

Introduction: The long term use of opioid analgesics limited due to the developing tolerance and their adverse effects. One of the reasons for the tolerance incidence to morphine is the production of pro-inflammatory cytokines. In this study, to investigate the association between the effects of Marrubium parviflorum and the incidence of opioid tolerance, chronic administration of methanolic extract of aerial parts that containing anti-inflammatory and antioxidant effects was used. Aim: The aim of this study was to investigate the effects of chronic administration of methanolic extract of aerial parts of Marrubium parviflorum on developing tolerance to analgesic effect of morphine in male rats. Method: aerial parts of M. parviflorum were Soxhlet extracted respectively with Petroleum ether, Chloroform and MeOH. Seven male rat groups were studied in this study, which included: the group received morphine (10mg/kg) + normal saline (1ml/kg), morphine + vehicle (1ml/kg, 10% DMSO) , morphine + three different doses of M. parviflorum extract (10, 20, 40mg/kg), the most effective dose of M. parviflorum extract (40mg/kg) with normal saline and the group that received normal saline. At the beginning, after determining the base latency time, half an hour after intraperitoneal injection of drugs, a hot plate test was performed every other day. Result: In the group receiving morphine and the group receiving vehicle and morphine, tolerance was occurred on day 7 and in the groups receiving different doses of M. parviflorum extract (10, 20, 40 mg/kg) with morphine; tolerance was occurred on days 11, 13 and 17 respectively. Serologic malondialdehyde levels were lower in the groups that receiving the most effective dose of the extract than the morphine group and showed a significant difference (p <0.05). Conclusion: Methanolic extract of aerial parts of Marrubium parviflorum, significantly delayed the development of tolerance to the analgesic effect of morphine (p<0.05).