Antinociceptive tolerance to the mu-opioid agonist DAMGO is dose-dependently reduced by MK-801 in rats.
Antinociceptive tolerance to the mu-opioid agonist DAMGO is dose-dependently reduced by MK-801 in rats.
复制标题
MK-801 可以剂量依赖性地降低大鼠对 mu-阿片类激动剂 DAMGO 的抗伤害耐受性。
DOI：
10.1016/s0304-3940(98)00472-8
复制
发表时间：
1998
影响因子：
2.5
通讯作者：
Mayer,DJ
中科院分区：
文献类型：
--
作者：
Mao,J;Price,DD;Lu,J;Mayer,DJ
Morphine has been used in previous studies that investigate interactions between the spinal cord μ-opioid and N-methyl-d-aspartate (NMDA) receptors in mechanisms of antinociceptive tolerance. Although morphine acts primarily on the μ-receptor, it also activates other subtypes of opioid receptors. In the present study, the selective μ-opioid agonist, d-Ala2-N-Me-Phe4,Gly-ol5-enkephalin (DAMGO), was used to further test the hypothesis. Repeated intrathecal (i.t.) administration of 6 μg DAMGO (twice daily) in rats for 7 days resulted in an approximately 17-fold rightward shift of the cumulative dose–response curve (the tail-flick test) on Day 8 compared to that on Day 1. This rightward shift of the dose–response curve was prevented by the i.t. co-administration with DAMGO of the NMDA receptor antagonist MK-801 (10=5>2.5>>1.25 nmol>saline). Further, a lower dose range of MK-801 (2.5>1.25 nmol>0.625>0.313=saline) was effective to prevent the antinociceptive tolerance to a lower dose (1.5 μg) of DAMGO using the same i.t. administration regimen. Thus, the present results provide further evidence supporting a cellular and intracellular model of opioid tolerance involving interactions between the μ-opioid and the NMDA receptors in the spinal cord.
