The preventive effect of bee pollen methanolic extract on morphine-induced tolerance and dependence in male mice

Abstract

Introduction: The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. The mechanisms involved in the development of morphine tolerance and dependence include increased expression of P-glycoproteins and NMDA receptors, as well as activation of the oxidative stress system. Bee pollen, with its antioxidant effects and anti-inflammatory appears to have beneficial effects in preventing morphine tolerance and dependence.Aim: To evaluate the effects of bee pollen on morphine-induced tolerance and dependence in male mice.Methods: Fifty male mice (20–30 g) were randomly divided into 5 groups and subjected to the following regimens for 10 days: Saline control group, morphine control group, and three groups receiving bee pollen (12/5, 25, 50 mg/kg). On the eleventh day, following the acquisition of base latency time from the animals, morphine (9 mg/kg, ip) was administered, and the hot plate test was conducted over one hour. One hour after the hot plate test, naloxone (4 mg/kg, ip) was injected, and withdrawal symptoms (jumping and standing) were measured over 30 minutes. Blood samples were then collected, and the serum was separated to determine for the determination of serum levels of MDA and TAC. Results: Pretreatment by bee pollen, before morphine administration, decreased the development of tolerance to the antinociceptive action of morphine and also reduced naloxone-precipitated withdrawal jumps and standing on feet.Conclusion: Bee pollen (12/5, 25, 50 mg/kg, ip) reduces prevents morphine dependence and tolerance in animals, most likely due to its beneficial mechanisms through the inhibition of the oxidative stress system.