Vigabatrin attenuates the development and expression of tolerance to morphine-induced antinociception in mice

The efficacy of opioids is limited in chronic pain treatment, as a result of development of opioid tolerance. Based on previous demonstration of the effect of anticonvulsant drugs on morphine antinociception, the present study investigated the effects of vigabatrin (VGB) on the development and expression of morphine tolerance in mice. 101 male NMRI mice weighing 20-25 g were used in these experiments. To evaluate the VGB effects on the development or expression of morphine tolerance, animals received VGB (5, 10 or 20 mg/kg; i.p.), 30 min before morphine (50 mg/kg; s.c.) during induction period once daily for 3 days; or 30 min before challenge dose of morphine (5 mg/kg) before and after morphine-induced tolerance, respectively. The analgesic effect of VGB was evaluated at 30-time intervals (30, 60, 90 and 120 min) by tail-flick analgesiometer. The results showed that VGB at the dose of 20 mg/kg significantly attenuated the development and expression of morphine tolerance. Additionally, VGB alone did not affect the tail-flick latency times. Therefore, while VGB alone has no antinociceptive effect, it can prevent the development of morphine tolerance in mice.