Abstract

Tolerance development to the antinociceptive effect of morphine is a major concern of its long-term administration. Objectives: Based on previous studies on the effect of some anticonvulsant drugs on morphine tolerance, the present study investigated the effects of Levetiracetam (LEV) on the development and expression of morphine tolerance in mice. To evaluate the LEV effects on the development or expression of morphine tolerance, animals received LEV (60, 300 or 900 mg/kg), either 30 min before the injection of morphine (50 mg/kg) during induction period once daily for 3 consecutive days; or 30 min before injection of challenging dose of morphine (5 mg/kg), before and after morphine-induced tolerance, respectively. The analgesic effect of LEV was evaluated by tail-flick analgesiometer 30 min after injection. LEV at the doses of 300 and 900 mg/kg significantly attenuated the development of morphine tolerance, but had no effect on expression of morphine tolerance. High dose of LEV (900 mg/kg) alone had antinociceptive effect and significantly increased the tail-flick latency time which was attenuated by naloxone. LEV showed antinociceptive effect, and could prevent the development of tolerance presumably via opioid’s receptors. Co-administration of LEV and morphine may be of great clinical implication. © 2019, SILAE (Italo-Latin American Society of Ethnomedicine). All rights reserved.