EFFECTS OF KETAMINE AND MAGNESIUM ON MORPHINE INDUCED TOLERANCE AND DEPENDENCE IN MICE

The goal of this study was to evaluate the effects of ketamine and magnesium on prevention ofdevelopment of morphine tolerance and dependence in mice. In this study different groups of micereceived morphine (50 mg/kg, sc) + (saline 10ml/kg), morphine (50 mg/kg, sc) + ketamine (25,50 or 75mg/kg, ip), morphine (50 mg/kg, sc) + magnesium (10,20 or 40 mg/kg, ip), morphine (50 mg/kg, sc) +ketamine (25 mg/kg, ip) + magnesium (10 mg/kg, ip)] once a day for four days. Tolerance was assessedby administration of morphine (9 mg/kg, ip) and using hot plate test on fifth day. Withdrawal symptomswere assessed by administration of naloxone (4 mg/kg, ip) two hours after co-administration of morphinewith either ketamine or magnesium.It was found that pretreatment with ketamine or magnesium decreased the degree of tolerance anddependence. Additionally, co-administration of ketamine and magnesium before morphine administrationdecreased the tolerance and dependence significantly. From these results it may be concluded thatadministration of ketamine or magnesium alone or together could prevent the development of toleranceand dependence to the analgesic effects of morphine. These effects may be related to the N-Methyl-DAspartate(NMDA) receptor antagonist behavior of ketamine and the ability of magnesium to block theCa channel of NMDA receptors.