The effects of topiramate on the acquisition and expression of morphine-induced place conditioning and behavioral sensitization in mice

Introduction: Topiramate is a newly anti-convulsant drug, which acts as NMDA glutamate receptor antagonist as well as the GABAB receptor agonist. It is used for physical dependence to opioids as well as cocaine, nicotine, alcohol and ecstasy dependence. In the present study attempts were made to further identification of the effects of topiramate on the acquisition and expression of morphine-induced conditioned place preference and behavioural sensitisation in mice. Methods: Male Swiss-Webster mice were used. Conditioned place preference and locomotion were assessed by an un-biased place conditioning paradigm and open filed methods. In a pilot study, the effects of morphine and topiramate on place conditioning paradigm as well as locomotion were assessed in morphine-nave animals for evaluation of effective and ineffective doses of the drugs. Different doses of topiramate were injected to the animals 30 min before each morphine injections (acquisition) or 30 min before the experiments were beginning on the test day. Results: Administration of different doses of morphine (0.5, 5 and 50 mg/kg) induced locomotor activity in the animals. In addition, morphine (1, 10 and 20 mg/kg) administration also induced place preference. On the other hand, administration of different doses of topiramate (20, 80 and 120 mg/kg) neither induced place preference nor altered animals’ activity. Topiramate administration (20 and 80 mg/kg) and (80 and 120 mg/kg) reduced the acquisition and expression of morphine-induced place preference, respectively. In addition, topiramate (20, 80 and 120 mg/kg) reduced the acquisition of morphine-induced behavioral sensitization where as the drug in dose 80 mg/kg enhanced the expression of morphine-induced behavioral sensitization. Conclusion: It can be concluded that topirmate administration interacts with the euphoric and locomotor properties of morphine and this can be considered in therapeutic usage of the drug.