Evaluate the effect of chronic administration of Dimethyl fumarate on morphine withdrawal syndrome in rat

Abstract

Introduction: Long-term use of opioids is associated with the development of tolerance and dependence on them, in which several mechanisms have been proposed, including the occurrence of oxidative stress and increased production of inflammatory factors. Regarding dimethyl fumarate, the ability to increase the activity of antioxidant pathways and reduce the release of inflammatory chemical mediators such as TNF-α and IL-6 has been proven. Objective: To investigate the possible effect of chronic dimethyl fumarate consumption on morphine withdrawal symptoms in male rats. Materials and Methods: 15, 30, and 60 mg of dimethyl fumarate were prepared and used to investigate the pharmacological effects of chronic dimethyl fumarate on morphine withdrawal symptoms in male rats. Animals in 6 groups of eight, including group 1: morphine + saline, groups 2, 3, and 4: morphine with three different doses of dimethyl fumarate, group 5: carrier and morphine, and group 6: receive the most effective dose of morphine-free dimethyl fumarate. After morphine dependence of the animals (9-day injections of increasing doses of morphine), we recorded the symptoms of deprivation syndrome after naloxone injection in each group. The effect of dimethyl fumarate was also evaluated. After completing the behavioral studies, we anesthetized the mice, took blood samples, and measured MDA and TNF-α in different groups by ELISA test. Results: Dimethyl fumarate in doses of 15, 30, and especially 60 mg could significantly reduce the symptoms of morphine withdrawal syndrome (P <0.05). The 60 mg dose is the most effective in terms of the total score. Conclusion: Chronic administration of dimethyl fumarate with anti-inflammatory and antioxidant effects is effective in reducing withdrawal symptoms.