Inhibition of morphine withdrawal by the NMDA receptor antagonist MK-801 in rat is age-dependent

This study investigated the effects of the NMDA receptor antagonist MK-801 on the development of morphine dependence in 7-, 14-, and 21-day-old rat pu ps. For 6.5 days, starting at 1, 8, or 15 days of age, rats were pretreated with MK-801 (0.03 or 0.1 mg/kg, bid) or saline; 15 min later, morphine sul fate (10 mg/kg) or saline was injected to induce opiate dependence. On the afternoon of the seventh day, pups were injected with MK-801 (0.1 mg/kg) or saline and 15 min later with naltrexone (1 mg/kg) to precipitate withdrawa l. Pups were then placed in a warm chamber with the litter and their behavi or scan-sampled every 15 sec for a total of 15 min. MK-801 failed to inhibi t morphine withdrawal in the 7-day-old rat, but did attenuate the developme nt of morphine dependence in both the 14- and 21-day-old rats. These result s suggest that the NMDA receptor is not functionally active in opiate withd rawal until around the second to third week of postnatal life in the rat an d that there exists a transition period for the NMDA receptor to play a rol e in the development of opiate dependence and withdrawal. Synapse 40:282-29 3, 2001. (C) 2001 Wiley-Liss, Inc.