BLOCKADE OF TOLERANCE TO STRESS-INDUCED ANALGESIA BY MK-801 IN MICE

The N-methyl-D-aspartate (NMDA) receptor has been implicated in mechan isms of tolerance to morphine-induced analgesia. The present study exa mined the role of the NMDA receptor in the development of tolerance to stress-induced analgesia (SIA). In the first experiment, mice were ex posed to a stressor (a 3-min forced swim in water maintained at 32 deg rees C) once daily for 15 consecutive days. Analgesia was measured 2 m in after stress on the first and last day using the hot-plate test. To examine the role of the NMDA receptor in the development of tolerance to SIA mice were treated daily with the non-competitive NMDA receptor antagonist, MK-801, 15 min before swimming. Pretreatment with MK-801 was found to block both analgesia and tolerance. In a second experimen t, to examine whether SIA and tolerance to SIA are mediated by similar or different mechanisms, mice were injected daily with MK-801 after a nalgesia had dissipated (1 h following swim). Tolerance to SIA was blo cked by delayed injections of MK-801. These results suggest that the N MDA receptor is involved in mechanisms of tolerance to SIA, independen t of its role in analgesia. Copyright (C) 1997 Elsevier Science Inc.