Evaluation the effect of acute administration of ethanolic extract of Myristica fragrans seeds on morphine withdrawal syndrome in male rats

Abstract

Introduction: long-term consumption of morphine will cause tolerance and dependence. During morphine withdrawal syndrome, increasing in inflammatory factors and changes in activity of the receptors and level of the neurotransmitters in the CNS such as reducing dopamine has been proven. Myristica fragrans seed has effects on the inflammation process, gastrointestinal system and CNS. So it would probably be able to reduce morphine withdrawal signs. Objective: To evaluate the effect of acute administration of hydro alcoholic extract of Myristica fragrans seeds on morphine withdrawal syndrome in male rats. Methods: Hydro alcoholic extract of Myristica fragrans seeds in 3 doses (5, 10, 20 mg/kg) was dissolved in dimethyl sulfoxide 40% for pharmacologic studies on 56 wistar male rats (225-275 g) which were divided to 8 groups randomly. To induce dependence, morphine was injected with increasing (5, 10, 15, 20, 25 mg/kg) subcutaneous doses for 9 days twice a day. On the 9th day, 2 hours after morning dose of morphine, naloxone was administered intraperitonealy 4 mg/kg and withdrawal signs were recorded such as rearing, wet dog shake, genital grooming. In 3 groups, on 9 ͭʰ day, 1 hour after last dose of morphine, (5, 10, 20 mg/kg) of extract injected intraperitonealy and 1 hour later, naloxone was administered and withdrawal signs were recorded. Result and discussion: Our studies indicated that acute administration of hydro alcoholic extract of Myristica fragrans seeds decreased the severity of the most withdrawal behaviors and the total withdrawal score, (5 and 10 mg/kg ) of extract, significantly reduced TWS (p<0.001). Conclusion: This study indicated that the most effective dose for reducing the TWS, is ( 5 mg/kg) of hydro alcoholic extract of Myristica fragrans seeds.