Evaluation of the effect of chronic administration of Edaravone on the development of morphine dependence in male mice

Abstract

Introduction: Opioids as a class of medicines with analgesic effects have been applied intensively. Despite many achivments, the clinical use of opioid analgesics are restricted due to some problems such as tolerance, dependence, and addiction. It has been shown that various mechanisms such as stress oxidative and inflammatory systems play key roles in morphine dependence. Using the anti-oxidant drug in order to overcome morphine withdrawal syndrome seems interesting. The effects of edaravone with anti-oxidant propertise can be investigated on morphine withdrawal syndrome. Aim: Evaluation of the effect of chronic administration of edaravone on the development of morphine dependence in male mice.Method: Edaravone was prepared. The experiment was performed in five groups of 8 mice, so one group received eight days of morphine with normal saline as a drug carrier, one group received. The other three groups received three different doses of edaravone along with morphine. On the ninth day, withdrawal symptoms were recorded after naloxone injection and blood samples were examined for antioxidant factors. The MDA and TAC were evaluated. Results: The total withdrawal score in the treated group with the 8 and 16 mg/kg dose of edaravone with morphine (16 mg/kg) was significantly lower than the morphine-saline group (p<0.001). No significant sedative and locomotion activity reduction was observed in mice after using edaravone. Antioxidant evaluation tests showed that the level of MDA and TAC is reduced upon exposure by edaravone compared to the control group. Conclusion: Edaravone decreases the symptoms of morphine withdrawal syndrome. Based on results one may conclude it exerts activity via oxidative stressmechanism.