Evaluating the effect of dextromethorphan and bupropion administration on development of dependence to morphine in mice

Abstract

Chronic administration of opioids causes psychological and physiological dependency. Despite many researches, the exact mechanism of opioid addiction and withdrawal syndrome has not yet been fully understood. In this study, the effects of dextromethorphan and bupropion on the animal model of opioid dependency have been investigated.Purpose:The main objective of this study is to investigate the effect of chronic consumption of dextromethorphan and bupropion on the symptoms of morphine deprivation in male rats.Materials and methods:Dextromethorphan and bupropion were used to conduct experiments on male mice (20-30 grams), which were randomly divided into 11 groups of 10. First, they were treated with either normal saline or morphine for 2 weeks. During this period, different doses of dextromethorphan and bupropion or their combination were injected into each group every day half an hour before the daily injection of morphine. Subsequently, on the 14th day, two hours after morphine injection, naloxone was administered to the animals, and withdrawal symptoms were measured within half an hour. Thereafter, blood samples were obtained from their heart and serum levels of MDA and TAC was measured.Results:The results of this study showed that the injection of dextromethorphan reduced withdrawal symptoms. Additionally, when a combination of dextromethorphan and bupropion was injected, we observed significant effects (p-value < 0.05) compared to the injection of each of these drugs alone.Conclusion:In this study, the simultaneous injection of dextromethorphan and bupropion has superiority over the injection of each of the drugs alone. Part of this mechanism is likely related to the inhibition of dextromethorphan metabolism by bupropion. However, to understand the more precise mechanisms, we need further complementary studies.