Effect of five common anticonvulsant drugs on naloxone-precipitated morphine withdrawal in mice

This study was designed to assess the effect of five common anticonvulsant drugs on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Male mice (25-35 g) were made dependent by increasing doses of morphine (30-90 mg/kg). At least three doses of phenytoin, carbamazepine, sodium valproate, lamotrigine and topiramate were injected i.p. to morphine-dependent mice 45 min prior to induction of withdrawal syndrome by naloxone (5 mg/kg, i.p.). Control animals received vehicle. Number of jumpings was counted and ptosis, tremor, piloerection and diarrhea were checked in a 30 min period started just after naloxone injection. Results showed that lamotrigine, phenytoin and sodium valproate were ineffective in suppression of withdrawal syndrome while carbamazepine produced a dose-dependent reduction of jumpings. Topiramate at the maxium applied dose (100 mg/kg) significantly reduced number of naloxone-elicited jumpings. It seems that carbamazepine by inhibition of N-Methyl-D-Aspartate (NMDA) receptors and topiramate by inhibiting kainite-activated (AMPA) receptor antagonists suppress morphine withdrawal syndrome but further studies are needed to have a definite conclusion.