Evaluation of the Effects of Aerial Parts of Hydro-Alcoholic Extract of Tanacetum kotschyi and Dextromethorphan on Morphine Withdrawal Symptoms

Abstract

Background There are different mechanisms of dependence and tolerance to opioids. Dextromethorphan is a non-competitive N-Methyl-D-Aspartate (NMDA) glutamate receptor antagonist, whereas Tanacetum kotschyi (T. kotschyi) has antioxidant properties. Objectives This study investigates inhibitory effect of T. kotschyi extract and dextromethorphan on the incidence of morphine dependence in male mice. Materials and Methods 81 mice in 9 groups of 9 (weight: 20-30 g) were randomly selected and received drug regimens once a day for two weeks. Different doses of dextromethorphan (15, 30, 60 mg/kg, IP) and extract of T. kotschyi (25, 50, 100 mg/kg, IP) or both were injected half an hour before the daily injection of morphine (25 mg/kg, IP), then on the fourteenth day, two hours after morphine injection, naloxone (4 mg/kg, IP) was injected and withdrawal symptoms (number of jumps and standing on two legs) were measured within half an hour. After anesthetizing the animals, blood samples were collected from the heart to Measure Serum Malondialdehyde (MDA) and total Antioxidant capacity (TAC) levels. Results Dextromethorphan and T. kotschyi doses decreased the symptoms as well as co-injection of dextromethorphan (15 mg/kg) and T. kotschyi (25 mg/kg). Moreover, dextromethorphan doses and T. kotschyi (50 and 100 mg/kg) diminished MDA level with p<0.05. Comparing to T. kotschyi (25 mg/kg), the co-injection increased standing on feet and decreased number of jumping and MDA level. Conclusion T. kotschyi can be suggested as a new combination to reduce the symptoms of morphine withdrawal syndrome for further studies and to reduce the incidence of opioid addiction in communities.

Keywords: Dependence; Dextromethorphan; Morphine; Oxidative Stress; Tanacetum kotschyi