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慢性转轮活动会降低雄性和雌性大鼠对吗啡诱导镇痛的敏感性。

Chronic running-wheel activity decreases sensitivity to morphine-induced analgesia in male and female rats.

作者信息

Kanarek R B, Gerstein A V, Wildman R P, Mathes W F, D'Anci K E

机构信息

Tufts University Department of Psychology, Medford, MA 02155, USA.

出版信息

Pharmacol Biochem Behav. 1998 Sep;61(1):19-27. doi: 10.1016/s0091-3057(98)00059-8.

DOI:10.1016/s0091-3057(98)00059-8
PMID:9715803
Abstract

The effects of exercise on morphine-induced analgesia were examined in male and female Long-Evans rats. In Experiment 1, 10 male rats were housed in standard laboratory cages, and 10 in activity wheels for 20 days prior to nociceptive testing. Pain thresholds were assessed using a tail-flick (TF) procedure. Morphine sulfate was administered using a cumulative dosing procedure (2.5, 5.0, 7.5, 10.0, 12.5, and 15.0 mg/kg). TF latencies were measured immediately prior to and 30 min following each injection. In Experiment 2, morphine-induced analgesia was examined in females in an identical manner to that of Experiment 1. Additionally, to determine if the attenuation of morphine-induced analgesia was permanent or reversible, after the initial test nociceptive test, previously active female rats were placed in standard cages, and previously inactive females placed in running wheels for 17 days prior to a second nociceptive test. Baseline TF latencies were significantly shorter in active male rats than in inactive animals. Additionally, both active male and female rats displayed decreased morphine-induced analgesia relative to inactive controls. Moreover, females that had been inactive and then were permitted to run showed a suppression in morphine-induced analgesia relative to presently inactive rats, and to their own nociceptive responses when sedentary. In contrast, morphine-induced analgesia in initially active females who were housed in standard cages during part 2 of Experiment 2 was enhanced relative to their first nociceptive test and to presently active rats. Experiment 3 examined the effects of short-term (24 h) running on antinociception. Baseline TF latencies were shorter in active rats than inactive rats. However, no differences in morphine-induced analgesia were observed as a function of short-term exposure to exercise. Experiment 4 investigated whether differences in body weight contributed to the differences in morphine-induced analgesia between chronically active and inactive animals. %MPEs did not vary among male rats maintained at 100, 85, or 77% of their free-feeding body weight. These results indicate that chronic activity can decrease morphine's analgesic properties. These effects may be due to crosstolerance between endogenous opioid peptides released during exercise and exogenous opioids.

摘要

在雄性和雌性Long-Evans大鼠中研究了运动对吗啡诱导的镇痛作用的影响。在实验1中,10只雄性大鼠饲养在标准实验室笼子中,10只饲养在活动轮中,在进行伤害性测试前持续20天。使用甩尾(TF)程序评估疼痛阈值。采用累积给药程序(2.5、5.0、7.5、10.0、12.5和15.0mg/kg)给予硫酸吗啡。在每次注射前及注射后30分钟测量TF潜伏期。在实验2中,以与实验1相同的方式研究雌性大鼠吗啡诱导的镇痛作用。此外,为了确定吗啡诱导的镇痛作用减弱是永久性的还是可逆的,在初次测试伤害性测试后,将先前活跃的雌性大鼠置于标准笼子中,将先前不活跃的雌性大鼠置于活动轮中17天,然后进行第二次伤害性测试。活跃雄性大鼠的基线TF潜伏期明显短于不活跃动物。此外,相对于不活跃对照组,活跃的雄性和雌性大鼠均表现出吗啡诱导的镇痛作用降低。此外,先前不活跃然后被允许运动的雌性大鼠相对于目前不活跃的大鼠以及它们久坐时的伤害性反应,显示出吗啡诱导的镇痛作用受到抑制。相比之下,在实验2的第2部分中饲养在标准笼子中的最初活跃的雌性大鼠,其吗啡诱导的镇痛作用相对于它们的第一次伤害性测试以及目前活跃的大鼠有所增强。实验3研究了短期(24小时)运动对镇痛作用的影响。活跃大鼠的基线TF潜伏期比不活跃大鼠短。然而,未观察到短期运动暴露对吗啡诱导的镇痛作用有差异。实验4研究了体重差异是否导致长期活跃和不活跃动物之间吗啡诱导的镇痛作用差异。维持在自由摄食体重的100%、85%或77%的雄性大鼠之间的%MPEs没有变化。这些结果表明,长期运动可以降低吗啡的镇痛特性。这些作用可能是由于运动过程中释放的内源性阿片肽与外源性阿片类药物之间的交叉耐受性。

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