Enhancement of morphine actions in morphine-naive and morphine-tolerant mice by LY 235959, a competitive antagonist of the NMDA receptor.

1. The effects of LY 235959, a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the analgesic and hypothermic actions of morphine, were determined in nontolerant and morphine-tolerant mice. 2. LY 235959 enhanced the analgesic and hypothermic action of morphine in nontolerant mice. 3. LY 235959 also enhanced the analgesic and hypothermic actions of morphine in morphine-tolerant mice. LY 235959, injected before saline injection, had no effect on the antinociception or the body temperature. 4. It is concluded that competitive antagonism of the NMDA receptor enhances the pharmacologic actions of morphine both in morphine-naive and morphine-tolerant mice and that these actions differ from the noncompetitive antagonism of the NMDA receptors.