Evaluation of the effect of dimethyl fumarate and honey (Azerbaijan Siah Roud) on morphine induced tolerance in mice

Abstract

Previous studies have shown the influence of the glutaminergic system and oxidative stress in the development of morphine tolerance. Chronic use of opioids causes tolerance to their analgesic effects. The present study examines the effects of dimethyl fumarate and natural honey on morphine-induced tolerance in mice. Aim: To investigate the effects of dimethyl fumarate and natural honey on morphine-induced tolerance in mice. Materials and Methods: Ten groups of male mice (n=9 in each group, weight = 20-30g) were administrated the following daily regimens for 14 days: 1) Saline (10 ml/kg, ip)+ Saline (10 ml/kg, ip) 2) Saline (10 ml/kg, ip)+ Morphine(25mg/kg, ip) 3,4,5) Dimethyl fumarate (10,20,40 mg/kg, ip )+ Morphine (25mg/kg, ip) 6,7,8) Honey (100, 200, 400mg/kg, ip )+ Morphine (25mg/kg, ip) 9) Dimethyl fumarate (20mg/kg, ip)+ Honey (100 mg/kg, ip)+ Morphine (25mg/kg, ip) 10)DMSO 20%(10mg/kg, ip)+ Morphine (25mg/kg, ip) Then, on the 15th day, the analgesic effects caused by the morphine test dose (9mg/kg, ip) were investigated in different groups by the hot plate method.Then blood sampling was performed. Plasma serums were provided and stored in -70 c until MDA and TAC assays with relevant kits.Results: Administration of dimethyl fumarate (10, 20, and 40 mg/kg, ip) and honey (100, 200, 400 mg/kg, ip) causes a significant decrease in tolerance to morphine.Conclusion: Different doses of honey and dimethyl fumarate caused a decrease in tolerance to morphine by affecting the oxidative stress system, but a significant difference in the form of increased tolerance was seen in the combined injection.