Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat
Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat
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DOI：
10.1016/j.brainres.2005.04.001
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发表时间：
2005-06-14
期刊：
影响因子：
2.9
通讯作者：
Morgan, MM
中科院分区：
文献类型：
--
作者：
Lane, DA;Morgan, MM
反复给药吗啡已被证明产生对吗啡的抗痛觉作用的耐受性。然而，反复服用吗啡降低抗痛觉的程度被反复的行为测试夸大了，这种现象被称为行为耐受性。一个重要的问题是，是否可以通过将吗啡直接注入腹外侧导水管周围灰质（vPAG）来克服行为耐受，vPAG是吗啡抗痛觉的关键结构。大鼠分别在vPAG（实验1）或皮下注射吗啡或生理盐水（实验2），20 min后进行热板测试。对照组接受同样的药物治疗，但没有进行伤害性测试。无论是静脉注射吗啡还是全身注射吗啡，反复的伤害性试验或反复给药均产生抗伤害性耐受性。给予高剂量吗啡（20mg /kg, s.c）能够克服行为耐受的发展，但不能克服药物耐受，这揭示了这两种类型的耐受的不同机制。这些数据表明行为耐受性与吗啡给药途径无关。(c) 2005 Elsevier B.V.版权所有
Repeated morphine administration has been shown to produce tolerance to the antinociceptive effects of morphine. However, the degree to which repeated morphine administration decreases antinociception is exaggerated by repeated behavioral testing, a phenomenon known as behavioral tolerance. An important question is whether behavioral tolerance can be overcome by direct administration of morphine into the ventrolateral periaqueductal gray (vPAG), a key structure contributing to morphine antinociception. Rats were injected with morphine or saline into the vPAG (Experiment 1) or subcutaneously (Experiment 2) followed 20 min later with hotplate testing. The control groups received the same drug administration, but no nociceptive testing. Repeated nociceptive testing or repeated morphine administration produced antinociceptive tolerance regardless of whether morphine was injected into the vPAG or systemically. Administration of a high dose of morphine (20 mg/kg, s.c.) was able to overcome the development of behavioral tolerance, but not pharmacological tolerance revealing separate mechanisms for these two types of tolerance. These data indicate that behavioral tolerance is independent of the route of morphine administration. (c) 2005 Elsevier B.V. All rights reserved.