Marek P, Ben-Eliyahu S, Vaccarino A L, Liebeskind J C
Department of Psychology, University of California, Los Angeles 90024.
Brain Res. 1991 Aug 30;558(1):163-5. doi: 10.1016/0006-8993(91)90736-f.
To investigate the possible involvement of enduring or delayed changes at the N-methyl-D-aspartic acid (NMDA) receptor in the mechanisms of morphine tolerance, rats were treated with the specific NMDA receptor antagonist, MK-801 (0.15 mg/kg) 2 h after morphine injection (20 mg/kg) during a 4-day induction period of tolerance. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by MK-801. These findings suggest that long-lasting or delayed changes at the NMDA receptor underlie the development of morphine tolerance. Moreover, because MK-801 was delivered 2 h after morphine and therefore could not serve as a cue for morphine administration, these findings indicate that the attenuating effect of MK-801 on the development of morphine tolerance is not attributable to state-dependent learning.
为研究N-甲基-D-天冬氨酸（NMDA）受体的持续性或延迟性变化在吗啡耐受性机制中的可能作用，在为期4天的耐受性诱导期内，于吗啡（20mg/kg）注射后2小时，给大鼠注射特异性NMDA受体拮抗剂MK-801（0.15mg/kg）。在第5天，仅给大鼠注射吗啡（15mg/kg），并使用热板试验评估镇痛效果。MK-801可显著降低吗啡耐受性。这些发现表明，NMDA受体的长期或延迟变化是吗啡耐受性形成的基础。此外，由于MK-801在吗啡注射2小时后给药，因此不能作为吗啡给药的线索，这些发现表明MK-801对吗啡耐受性形成的减弱作用并非归因于状态依赖性学习。
