• Evaluation the Effect of chronic and acute administration of pregabalin on morphine withdrawal syndrome in rats
  • Lida Khodavirdilou,1,* Zahra Mehdilou,2
    1. Tabriz University of Medical Science
    2. Tabriz University of Medical Science


  • Introduction: Effect on excitatory neurotransmitters such as glutamate, P substance is one of the important analgesia mechanisms of morphine. After abrupt discontinuation of morphine consumption, the number of neurotransmitters increases after a while. Pregabalin is evaluated in this study with the hypothesis of reduction of excitatory neurotransmitters.
  • Methods: Experiments were implemented on rats weighing between 225 and 275 g. in order to create a dependency, morphine injection was performed nine days at doses of 5 mg (Day 1), 10 mg (Day 2 and 3), 15 mg (Day 4 and 5), 20 mg (Day 6 to 7) and 25 mg (Day 8 and 9) per kg subcutaneously twice a day. On the morning of the ninth day, two hours after morphine injection, naloxone was injected at a dose of 4 mg per kg per body weight and was also administrated intraperitoneally, and then signs of withdrawal syndrome such as jumping, movements like a wet dog were recorded for 45 minutes. In the groups treated with pregabalin(acute) medicine after injection of morphine, the medicine was injected in three doses of 10, 5, and 2.5 mg per kg of body weight through the intraperitoneal method ninth day and an hour after injecting the last dose of morphine. In chronic use, after daily morphine injection, the drug was dissolved in the carrier at doses (10,20,40 mg/kg) and administered half an hour after morphine injection.
  • Results: According to the recorded results, In case of acute use in doses of 10 and 5 mg/kg (p <0.001) and in case of chronic use in two doses 40.20 mg/kg (p <0.001) compared to the control group (morphine) most of the symptoms such as jumping, gestures like wet dog, teeth chattering were less severe.
  • Conclusion: The results show that pregabalin in both acute and chronic methods, in these two doses, significantly reduced the symptoms of morphine withdrawal syndrome.
  • Keywords: pregabalin, withdrawal syndrome, morphine.