Blockade of tolerance to stress-induced analgesia by MK-801 in mice.
The N-methyl-D-aspartate (NMDA) receptor has been implicated in mechanisms of tolerance to morphine-induced analgesia. The present study examined the role of the NMDA receptor in the development of tolerance to stress-induced analgesia (SIA). In the first experiment, mice were exposed to a stressor (a 3-min forced swim in water maintained at 32 degrees C) once daily for 15 consecutive days. Analgesia was measured 2 min 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 experiment, to examine whether SIA and tolerance to SIA are mediated by similar or different mechanisms, mice were injected daily with MK-801 after analgesia had dissipated (1 h following swim). Tolerance to SIA was blocked by delayed injections of MK-801. These results suggest that the NMDA receptor is involved in mechanisms of tolerance to SIA, independent of its role in analgesia.
Vaccarino
A L
AL
Department of Psychology, University of New Orleans, LA 70148, USA.
Clavier
M C
MC
D000698:Analgesia / Q000379:methods*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013312:Stress, Physiological / Q000188:drug therapy*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate