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.