اثر دو گانه توپيرامات بر تحمل حركتي ناشي از مورفين در موش هاي كوچك آزمايشگاهي نر

Dual effects of topiramate on tolerance to morphine-induced locomotors activity in small laboratory male mice

AIMS. Topiramate is an anti-convulsing drug, which produced its effects via glutamate metabotropic receptors inhibition and/or GABA receptor excitation. Previous studies indicated that both glutamate and GABAsystems have a role in morphine tolerance. In the present study, attempts were made to investigate the effects of topiramate on the tolerance to morphine-induced locomotors activity in male mice. METHODS, Male N-MARl mice (20-30 g) were used in this study by open field method. In a pilot study, ineffective doses of the drugs were determined. Then the animals became tolerant to morphine (50 mg/kg; Twice a day for three consecutive days) and their locomotors activity were calculated. Different doses of topiramate were administered to the animals 30 minutes before each morphine injection during tolerance development or on the test day 30 minutes before the experiments begining. RESULTS. Injection of morphine in order to develop tolerance. abolished the locomotors activity induced by effective dose of morphine. Injection of topiramate reduced the acquisition but enhanced the expression of morphine tolerance. Topirarnate by itself reduced the locomotors activity in morphine-nave animals. CONCLUSION. Topirmate administration leads to inhibition of acquisition but exagerates expression of tolerance to morphine-induced locomotors activity in male mice. It may be due to glutamate and/or GABAergic mechanisms. In addition, topirarnate by itself reduces the locomotors activity in animals.