Short-acting NMDA receptor antagonist MRZ 2/576 produces prolonged suppression of morphine withdrawal in mice

The present study sought to evaluate the timecourse of the effects of a sho rt-acting glycine site NMDA receptor antagonist, MRZ 2/576 (half-life of ab out 20 min), on the expression of morphine withdrawal syndrome in mice. Mor phine-naive and morphine-dependent mice (10-100 mg/kg, b.i.d., s.c., 9 days ) were injected with a combination of naltrexone (vehicle or 1 mg/kg, s.c.) and MRZ 2/576 (vehicle, 0.3-10 mg/kg, i.p.) 24 h after the last morphine i njection. MRZ 2/576 suppressed expression of several signs of morphine with drawal (jumping, shaking, forelimb tremor). Effects of MRZ 2/576 were equal ly expressed throughout 1-h observation test of both spontaneous and naltre xone-facilitated withdrawal. These results suggest that despite its short h alf-life, MRZ 2/576 produces prolonged suppression of morphine withdrawal s yndrome and this effect cannot be attributed to repeated morphine-induced i ncrease in sensitivity to naltrexone.