INHIBITORY EFFECT OF NITRIC-OXIDE (NO) SYNTHASE INHIBITORS ON NALOXONE-PRECIPITATED WITHDRAWAL SYNDROME IN MORPHINE-DEPENDENT MICE

The effect of intraperitoneally administered nitric oxide (NO) synthas e inhibitors has been examined on the naloxone-precipitated withdrawal syndrome in morphine-dependent mice. L-NAME (30-200 mg/kg) and L-NOAR G (7.5-50 mg/kg) induced a significant decrease of naloxone-precipitat ed withdrawal jumping and diarrhoea. However, L-NMMA (3.5-100 mg/kg), considered as a less potent NO synthase inhibitor, did not significant ly affect the withdrawal signs in mice. Although a specificity of NO s ynthase inhibitors is not fully established, these results indicate th at inhibition of NO synthesis in the central nervous system and periph ery may significantly affect the morphine withdrawal phenomena. Accord ingly, this study suggests an involvement of NO in morphine withdrawal syndrome.