MK-801 inhibits the development of morphine tolerance at spinal sites

Brain Res. 1993 Oct 29;626(1-2):332-4. doi: 10.1016/0006-8993(93)90597-g.


The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 has been shown to attenuate tolerance development in rats. In this study, we show that MK-801 inhibits tolerance to the antinociceptive effects of morphine, as assessed by the tail-flick test, in spinalized rats. These results suggest that NMDA receptor antagonists inhibit opiate tolerance at spinal sites, and also provide strong evidence that the effects of MK-801 are not due to its ability to interfere with associative learning, but instead to inhibition of non-associative mechanisms of opiate tolerance.

Publication types

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

MeSH terms

  • Animals
  • Dizocilpine Maleate / pharmacology*
  • Drug Tolerance
  • Male
  • Morphine / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Spinal Cord / drug effects*


  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Morphine