Evaluation the effect of chronic administration of Clinopodium umbrosum aerial parts methanol extract on the development of tolerance to morphine analgesia in mice

Abstract

Introduction: The long term use of opioid analgesics is limited due to the development of tolerance and their adverse effects. One of the reasons for the the tolerance incidence to morphine is the activity of glial cells and the production of pro-inflammatory cytokines. Aim: The effect of C. umbrosum extract on morphine tolerance in mice. Method: Extracted from the shoot of C. umbrosum after pulverization. After examining the composition of the extract, the experiment was performed in five groups of 8 mice, so that one group received morphine with normal saline as an extract carrier, one group received the extract alone without morphine with normal saline. The other three groups received three different doses of the extract along with morphine. At the beginning, after determining the base latency time, half an hour after intraoritoneal injection of drugs, a hot plate test was performed every other days. After the completion of the injection periods, blood was taken from the heart of the mice and the blood samples were analyzed for antioxidant factors.Results: In the group receiving morphine and saline (extract carrier) on day 9, and in the groups receiving doses of 10 and 20 mg/kg extract along with morphine on days 15 and 17, respectively, tolerance was established. In the group receiving a dose of 40 mg/kg extract, the responses were very variable from the first day and could not be interpreted. In the group receiving only extract with saline, no analgesic effect was observed. Also, the serum levels of MDA and TAC were higher in the groups receiving different doses of the extract compared.Conclution: In the groups receiving two doses of 10 and 20 mg/kg methanolic extracts of C. umbrosum delayed the tolerance to morphine and at the same time significantly increased the total antioxidant capacity (TAC) of the serum.