Objective: In the present study attempts were made to further identify the effects of topiramate on the acquisition and expression of morphine-induced conditioned place preference in morphine-sensitized mice.Materials and Methods: Male Swiss-Webster mice (20-30 g) were used in this study and un-biased place conditioning paradigm was applied for this purpose. In a pilot study, the effects of morphine on place conditioning paradigm were assessed in morphine-nave animals for evaluation of ineffective doses of the drug.Results: Administration of one dose daily morphine (5 mg/kg) for 3 days followed by five days rest, in order to develop Sensitization, enhanced the conditioning induced by ineffective morphine (0.25, 0.5 and 1 mg/kg). Injections of topiramate (20, 80 and 120 mg/kg, i.p.) reduced both the acquisition and expression of morphine CPP in morphinesensitized animals. Topiramate (20, 80 and 120 mg/kg, i.p.) by itself did not induce place preference or place aversion in the mice.Conclusion: It can be concluded that to piramate administration leads to inhibition of morphine Sensitization, which may be due to glutamate and/or GABAergic mechanisms. In addition, it seems that topiramate may be useful for treatment of psychological dependence to opioids.