Antinociceptive tolerance to the mu-opioid agonist DAMGO is dose-dependently reduced by MK-801 in rats

被引:35
|
作者
Mao, JR [1 ]
Price, DD [1 ]
Lu, J [1 ]
Mayer, DJ [1 ]
机构
[1] Virginia Commonwealth Univ, Med Coll Virginia, Dept Anesthesiol, Richmond, VA 23298 USA
关键词
mu-opioid receptor; tolerance; D-Ala(2)-N-Me-Phe(4); Gly-ol(5)-enkephalin; morphine; N-methyl-D-aspartate receptor; MK; 801;
D O I
10.1016/S0304-3940(98)00472-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Morphine has been used in previous studies that investigate interactions between the spinal cord mu-opioid and N-methyl-D-aspartate (NMDA) receptors in mechanisms of antinociceptive tolerance. Although morphine acts primarily on the cc-receptor, it also activates other subtypes of opioid receptors. In the present study, the selective mu-opioid agonist, D-Ala(2)-N-Me-Phe(4),Gly-ol(5-)enkephalin (DAMGO), was used to further test the hypothesis. Repeated intrathecal (i.t.) administration of 6 mu g 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. coadministration 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 mu g) 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 mu-opioid and the NMDA receptors in the spinal cord. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:193 / 196
页数:4
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