L-Nitroarginine methyl ester attenuates the development of morphine tolerance and dependence in mice

Abstract

The effect of the nitric oxide (NO) synthase inhibitor L-N G - nitroarginine methyl ester (L-NAME) on the morphine-induced analgesia, as well as on the morphine tolerance and dependence was examined in male albino Swiss mice. Neither acute nor repeated administration of L-NAME affected the morphine analgesia, as measured by a hot plate (HP) and a tail-flick (TF) tests. On the other hand, administration of L-NAME (10 mg/kg i.p.) jointly with morphine prevented the development of tolerance to the analgesic effect of morphine. L-NAME also attenuated the morphine dependence, as assessed by naloxone (2 mg/kg)-precipitated withdrawal. These results indicate that NO may play a crucial role in the development of morphine tolerance and dependence.