Estrous cycle stage-dependent expression of acute tolerance to morphine analgesia in rats
Estrous cycle stage-dependent expression of acute tolerance to morphine analgesia in rats
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DOI：
10.1016/j.ejphar.2004.01.012
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发表时间：
2004-02-23
影响因子：
5
通讯作者：
Bespalov, AY
中科院分区：
文献类型：
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作者：
Shekunova, EV;Bespalov, AY
基线疼痛敏感性和抗痛觉性治疗的反应对动物的性别和发情周期阶段都很敏感。在反复接触阿片类药物（如吗啡）引起的抗痛觉耐受性的发展中也观察到性别差异。传统的耐受性研究方案不评估发情周期阶段的影响。本研究旨在通过甩尾试验比较雄性和雌性（循环和去卵巢）Wistar大鼠对吗啡诱导的抗痛感急性耐受的发展。通过连续两次皮下注射吗啡（10 mg/kg）或间隔6 h的生理盐水诱导急性耐受，发现吗啡预处理大鼠对第二次吗啡剂量耐受。在发情的雌性大鼠中，耐受性最为明显，在雄性大鼠中，耐受性程度较低。在去卵巢大鼠以及发情期、退潮期和退潮期均不存在。因此，发情周期对吗啡诱导的抗痛觉性急性耐受的诱导有显著影响。这些结果表明，疼痛管理策略可以通过使用特定的性和动情周期技术来优化。(C) 2004 Elsevier B.V.版权所有
Both baseline pain sensitivity and the response to antinociceptive treatment are sensitive to an animal's sex and estrous cycle stage. Sex differences are also observed in the development of antinociceptive tolerance induced by repetitive exposure to opiate drugs such as morphine. Conventional tolerance study protocols do not assess the impact of the estrous cycle stage. The present study aimed to compare the development of acute tolerance to morphine-induced antinociception in male and female (cycling and ovariectomized) Wistar rats using the tail-flick test. Acute tolerance was induced by two consecutive subcutaneous injections of morphine (10 mg/kg) or saline separated by an interval of 6 h. It was found that rats pretreated with morphine were tolerant to the second morphine dose. Tolerance was most pronounced in proestrous female rats and, to a lesser degree, in male rats. It was absent in ovariectomized rats as well as during the estrus, metestrus and diestrus phases. Thus, the estrous cycle exerts dramatic effects on the induction of acute tolerance to morphine-induced antinociception. These results suggest that pain management strategies can be optimized through the use of sex- and estrous cycle-specific techniques. (C) 2004 Elsevier B.V. All rights reserved.