Suppressive effects of lamotrigine on the development and expression of tolerance to morphine-induced antinociception in the male mouse

Previous studies have demonstrated that some anticonvulsant drugs can modulate tolerance to the opioid analgesia. In the present study, the effects of lamotrigine (LTG) on the development and expression of tolerance to the morphine-induced antinociception were evaluated using tail-flick test. To assess the LTG effects on tolerance development, the animals received LTG (3, 10 or 30 mg/kg; i.p.), 30-min prior to morphine (50 mg/kg; s.c.) administration during tolerance induction period once daily for 3 days. Also, to evaluate the effects of LTG on tolerance expression, different doses of LTG were administered 30-min before challenge dose of morphine (4 mg/kg; s.c.) following morphine-induced tolerance. In each experiment the antinociceptive response to the challenge dose of morphine was evaluated before (on day 1) and after tolerance induction (on day 4) every 30-min till 2 h by tail-flick test. Furthermore, the analgesic effect of various doses of LTG alone or with the challenge dose of morphine was evaluated as well. The results showed that LTG at the doses of 10 and 30 mg/kg could inhibit the development of tolerance. Also, LTG at the dose of 30 mg/kg attenuated the expression of morphine-induced tolerance. LTG alone injection was associated significantly with higher latency period when compared to the control group. Moreover, LTG (10 and 30 mg/kg) significantly enhanced antinociceptive effect of morphine challenge dose in non-tolerant animals. These data indicated that, while LTG can attenuate both development and expression of morphine-induced tolerance, it can enhance morphine-induced antinociception. These effects may have important clinical implications.