MK-801 inhibits the development of morphine tolerance at spinal sites.
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.
Gutstein
H B
HB
Department of Anesthesiology, University of Michigan, Ann Arbor 48109-0800.
Trujillo
K A
KA
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine