Vaccarino A L, Clavier M C
Department of Psychology, University of New Orleans, LA 70148, USA.
Pharmacol Biochem Behav. 1997 Mar;56(3):435-9. doi: 10.1016/s0091-3057(96)00235-3.
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.
N-甲基-D-天冬氨酸（NMDA）受体与吗啡诱导的镇痛耐受性机制有关。本研究探讨了NMDA受体在应激诱导镇痛（SIA）耐受性形成中的作用。在第一个实验中，小鼠连续15天每天暴露于应激源（在32摄氏度的水中进行3分钟强迫游泳）。在第一天和最后一天应激后2分钟，使用热板试验测量镇痛效果。为了研究NMDA受体在SIA耐受性形成中的作用，在游泳前15分钟，每天用非竞争性NMDA受体拮抗剂MK-801处理小鼠。发现用MK-801预处理可阻断镇痛和耐受性。在第二个实验中，为了研究SIA及其耐受性是否由相似或不同的机制介导，在镇痛消散后（游泳后1小时），每天给小鼠注射MK-801。延迟注射MK-801可阻断SIA耐受性。这些结果表明，NMDA受体参与了SIA耐受性机制，与其在镇痛中的作用无关。
