Inhibition of Morphine Withdrawal by the NMDA Receptor Antagonist MK-801 in Rat Is Age-Dependent

Synapse. 2001 Jun 15;40(4):282-93. doi: 10.1002/syn.1051.


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 pups. 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 sulfate (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 withdrawal. Pups were then placed in a warm chamber with the litter and their behavior scan-sampled every 15 sec for a total of 15 min. MK-801 failed to inhibit morphine withdrawal in the 7-day-old rat, but did attenuate the development of morphine dependence in both the 14- and 21-day-old rats. These results suggest that the NMDA receptor is not functionally active in opiate withdrawal until around the second to third week of postnatal life in the rat and that there exists a transition period for the NMDA receptor to play a role in the development of opiate dependence and withdrawal.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Morphine / pharmacology*
  • Morphine Dependence / drug therapy*
  • Morphine Dependence / metabolism
  • Morphine Dependence / physiopathology
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology


  • Excitatory Amino Acid Antagonists
  • Narcotic Antagonists
  • Narcotics
  • Receptors, N-Methyl-D-Aspartate
  • Naltrexone
  • Dizocilpine Maleate
  • Morphine