Development of Morphine Induced Tolerance and Withdrawal Symptoms is Attenuated by Lamotrigine and Magnesium Sulfate in Mice

Abstract

The goal of this study was to evaluate the effects of lamotrigine and magnesium sulfate on morphine induced tolerance and withdrawal symptoms in mice. Different groups of mice were received morphine (30 mg kg(-1), s.c.) or morphine (30 mg kg(-1), s.c.)+lamotrigine (10, 20, 30 or 40 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) + magnesium sulfate (20, 40 or 60 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) + [lamotrigine (10 mg kg(-1), i.p.) + magnesium sulfate (20mg kg(-1), i.p.)] daily for 4 days. Tolerance was assessed using hot plate after administration of a test dose of morphine (9 mg kg(-1), i.p.) on fifth day. Withdrawal zsymptoms (Jumping and Rearing) were assessed by administration of naloxone (5 mg kg(-1), i.p.) 2 h after the last dose of morphine in fourth day. It was found that administration of lamotrigine or magnesium sulfate or their combination decreased the morphine induced tolerance and withdrawal symptoms. From these results it is concluded that lamotrigine and magnesium sulfate alone or in combination could prevent the development of morphine tolerance and withdrawal symptoms. Glutamate release inhibitory effect of lamotrigine and its possible mechanism and property of magnesium, blocking the N-Methyl-D-Aspartate (NMDA) receptor calcium channel, is probably its mechanism on preventing morphine induced tolerance and dependence.