Evaluating the effects of chronic administration of natural honey on the development of dependence to morphine in male rat

Abstract

Various mechanisms are involved in the development of opioid dependency, which include activation of the glutamatergic and dopaminergic systems and increased the pro-inflammatory cytokines and oxidative stress incidence. Also, previous studies indicated that the antioxidant capacity and anti-inflammatory effect of natural honey. Aim: The aim of this study was to evaluate the effects of chronic administration of natural honey on the development of dependence to morphine in male rat. Materials and methods: Natural honey (NHO) was prepared from Tarom Oliya region of Zanjan city. Experiments were performed on male Wistar rats weighing 225-275 g, divided into six groups (n=8) randomly. The study groups including: the morphine group, the three groups receiving morphine with honey at doses (200,400 and 800 mg/kg, i.p), the morphine-vehicle group, and the saline group. To creat morphine-dependency, injection of additive doses of morphine subcutaneously for 9 days were used. On the 9th day, one hour after the morning dose of morphine, naloxone (4mg/kg, i.p.) was injected and symptoms of withdrawal syndrome were counted for 60 minutes. Then, blood samples were taken for measuring TNF-α and MDA. To compare the results, one way ANOVA and Tukey test were used. P <0.05 was considered significant. Results: The results of this study showed that intraperitoneal injection of honey in 3 doses (200, 400 and 800 mg / kg with p <0.001) could significantly decrease the total score of the symptoms compared with the morphine-vehivle control group. NHO could significantly decrease TNF-α at dose 400 mg / kg with p >0.001 but did not affect MDA. Conclusion: Our results indicated that chronic administration of NHO had beneficial effects in reducing morphine withdrawal syndrome, and this effect is probably due to the anti-inflammatory effect of flavonoids in honey.