Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen(2), D-Pen(5)] enkephalin in mice
Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen(2), D-Pen(5)] enkephalin in mice
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DOI：
10.1016/s0196-9781(97)00021-1
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发表时间：
1997-01-01
期刊：
影响因子：
3
通讯作者：
Zhao, GM
中科院分区：
文献类型：
--
作者：
Bhargava, HN;Cao, YJ;Zhao, GM
本实验观察了神经元型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑（7-NI）对吗啡、U-50、488 H和δ-（[D-Pen（2），D-Pen（5）]脑啡肽，DPDPE）阿片受体激动剂抗伤害性作用的耐受性。通过每天两次注射吗啡（20 mg/kg，SC）、U-50，488 H（25 mg/kg，IF）或DPDPE（20 μ g/小鼠，ICV）4天使雄性Swiss-Webster小鼠耐受。当在第5天测试时，与注射载体的小鼠相比，对它们的抗伤害感受活性的耐受性通过慢性药物处理的小鼠中的降低的反应来证明。同时给予7-NI（20，40或80 mg/kg，IF）与DPDPE并没有改变对DPDPE的抗伤害性作用的耐受性的发展。然而，7-NI（40或80 mg/kg，IF）抑制对吗啡和U-50，488 H的抗伤害性活性的耐受的形成，但较低剂量的7-NI（20 mg/kg，IF）不起作用。长期给予7-NI本身并不改变对吗啡、U-50、488 H或DPDPE的急性反应。可以得出结论，nNOS的特异性抑制剂可以抑制耐受性的抗伤害性活动的μ-和κ-，但不是δ-阿片受体激动剂在小鼠中。(C)1997年爱思唯尔科学公司
The effects of 7-nitroindazole (7-NI), an inhibitor of the neuronal nitric oxide synthase (nNOS) which does not increase blood pressure, on tolerance to the antinociceptive activity of mu-(morphine), kappa-(U-50,488H) and delta-([D-Pen(2), D-Pen(5)]enkephalin, DPDPE) opioid receptor agonists were determined in mice. Male Swiss-Webster mice were made tolerant by twice daily injections of morphine (20 mg/kg, SC), U-50,488H (25 mg/kg, IF) or DPDPE (20 mu g/mouse, ICV) for 4 days. When tested on day 5, tolerance to their antinociceptive activity was evidenced by decreased response in chronic drug treated mice in comparison to vehicle-injected mice. Concurrent administration of 7-NI (20, 40 or 80 mg/kg, IF) with DPDPE did not modify the development of tolerance to the antinociceptive action of DPDPE. However, 7-NI (40 or 80 mg/kg, IF) inhibited the development of tolerance to the antinociceptive activity of morphine and U-50,488H but the lower dose of 7-NI (20 mg/kg, IF) was not effective. Chronic administration of 7-NI by itself did not modify the acute response to morphine, U-50,488H or DPDPE. It is concluded that a specific inhibitor of nNOS can inhibit tolerance to the antinociceptive activity of mu- and kappa- but not of delta-opioid receptor agonists in mice. (C) 1997 Elsevier Science Inc.