Evaluation of Effects of Dextrometorphan and Midazolam on Morphin-Induced Tolerance and Dependence in Mice

Long-term exposure to opiates induces physical dependence and tolerance. the main goal of this study was to evaluate the effects of dextro methorphan and midazolam and their combination on morphine tolerance and dependence in mice.different groups of mice were rendered randomly and received morphine (50mg/kg, sc), morphine (50 mg/kg, sc) + dextromethorphan (25,50 or 75 mg/kg, ip),morphine (50 mg/kg, sc) + midazolam (0.5, 1, 2 mg/kg, ip), morphine (50 mg/kg,sc) + dextromethorphan (25 mg/kg, ip) + midazolam (0.5 mg/kg, ip) once a day for four days. tolerance was assessed by administration of morphine (9 mg/kg, ip) onthe fifth day. withdrawal symptoms (markers for dependence) was assessed by administration of naloxone (4 mg/kg, ip) two hours after co-administration of morphine with either dextromethorphan or midazolam or their combination groups. results showed that pretreatment with dextromethorphan or midazolamdecreased the degree of tolerance and withdrawal symptoms significantly.additionally, co-administration of dextromethorphan and midazolam before morphineadministration decreased the tolerance and dependence but it was not significant.from these results, it may be concluded that dextromethorphan and midazolam aloneor in combination could prevent the development of tolerance and dependence tothe analgesic effects of morphine. these effects can be related to the n-methyl-daspartate(nmda) receptor antagonist behavior of dextromethorphan andgaba-receptor agonist behavior of midazolam.