Marek P, Ben-Eliyahu S, Gold M, Liebeskind J C
Department of Psychology, University of California, Los Angeles 90024.
Brain Res. 1991 Apr 26;547(1):77-81. doi: 10.1016/0006-8993(91)90576-h.
To investigate the possible role of excitatory amino acids (EAAs) in the mechanisms of morphine tolerance, rats were treated either with the wide-spectrum EAA antagonist, kynurenic acid (150 mg/kg), or the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist. MK-801 (0.05 mg/kg), during a four-day induction period of morphine tolerance. Morphine was given once daily at a dose of 15 mg kg. 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 both EAA antagonists. Control experiments showed that at the same doses neither acute nor chronic administration of these antagonists affected morphine analgesia itself in a manner that can explain these findings. The possible involvement of EAAs in the mechanisms of morphine tolerance is discussed.
为研究兴奋性氨基酸（EAAs）在吗啡耐受机制中可能发挥的作用，在吗啡耐受的四天诱导期内，对大鼠分别给予广谱EAA拮抗剂犬尿烯酸（150毫克/千克）或特异性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801（0.05毫克/千克）。吗啡以每日15毫克/千克的剂量给药一次。在第五天，仅给大鼠注射吗啡（15毫克/千克），并使用热板试验评估镇痛效果。两种EAA拮抗剂均显著降低了吗啡耐受性。对照实验表明，在相同剂量下，这些拮抗剂的急性或慢性给药均未以能够解释这些结果的方式影响吗啡本身的镇痛作用。文中讨论了EAAs可能参与吗啡耐受机制的情况。
