Delayed application of MK-801 attenuates development of morphine tolerance in rats

Przemyslaw Marek, Shamgar Ben-Eliyahu, Anthony L. Vaccarino, John C. Liebeskind

Research output: Contribution to journalArticlepeer-review

Abstract

To investigate the possible involvement of enduring or delayed changes at the N-methyl-d-aspartic acid (NMDA) receptor in the mechanisms of morphine tolerance, rats were treated with the specific NMDA receptor antagonist, MK-801 (0.15 mg/kg) 2 h after morphine injection (20 mg/kg) during a 4-day induction period of tolerance. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by MK-801. These findings suggest that long-lasting or delayed changes at the NMDA receptor underlie the development of morphine tolerance Moreover, because MK-801 was delivered 2 h after morphine and therefore could not serve as a cue for morphine administration, these findings indicate that the attenuating effect of MK-801 on the development of morphine tolerance is not attributable to state-dependent learning.

Original languageEnglish
Pages (from-to)163-165
Number of pages3
JournalBrain Research
Volume558
Issue number1
DOIs
StatePublished - 30 Aug 1991
Externally publishedYes

Keywords

  • Analgesia
  • MK-801
  • Morphine
  • N-Methyl-d-aspartic acid
  • State-dependent learning
  • Tolerance

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