Evaluation the effects of Topiramate and Citalopram on Morphine induced tolerance in male mice

Abstract

Introduction: Previous studies have shown the effect of glutamatergic system and oxidative stress on morphine tolerance. This study investigated the effects of Topiramate (an enhancer of GABAergic system activity and reducer of glutamatergic activity) and Citalopram (with antioxidant and anti-inflammatory effects) on the development of tolerance to analgesic effects of morphine. Aim: The main goal of this study was to investigate the effects of Topiramate and Citalopram on reducing the development of morphine ant nociceptive tolerance. Methods: Nine groups of male mice (n=8 in each group, weight = 20-30g) were administrated the following daily regimens for 4 days: 1) Saline (10ml/kg,ip) + Saline (10ml/kg,ip) 2) Saline (10ml/kg,ip) + Morphine (50mg/kg,ip) 3,4,5) Topiramate (12,34,48mg/kg,b.i.d,ip) + Morphine (50mg/kg,ip) 6,7,8) Citalopram (5,10,20mg/kg,ip) + Morphine (50mg/kg,ip) 9) Topiramate (12mg/kg,b.i.d,ip) + Citalopram (75mg/kg,b.i.d,ip) + Morphine (50mg/kg,ip) In the treatment groups, the drug was administered to the animals 30min before each morphine injections during tolerance development. On the fifty day, tolerance was assessed by administration of morphine (9mg/kg,ip) and using the Hot-plate test, conducted within one hour, at different time points (15,30,45,60min). Results: Significant reduction in morphine tolerance was observed by Topiramate (12,24,48mg/kg,bid.ip) and Citalopram (10,20mg/kg,b.i.d,ip). Co-administration of Topiramate (12mg/kg,b.i.d,ip) and Citalopram (5mg/kg,ip) also attenuated the degree of tolerance significantly. Conclusion: Based on these results, Topiramate and Citalopram may be decreased the development of tolerance to analgesic effects of morphine in a dose related manner