ONE OR 2 GENETIC-LOCI MEDIATE HIGH OPIATE ANALGESIA IN SELECTIVELY BRED MICE
ONE OR 2 GENETIC-LOCI MEDIATE HIGH OPIATE ANALGESIA IN SELECTIVELY BRED MICE
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DOI：
10.1016/0304-3959(94)00098-y
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发表时间：
1995-02-01
期刊：
影响因子：
7.4
通讯作者：
LIEBESKIND, JC
中科院分区：
文献类型：
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作者：
MOGIL, JS;MAREK, P;LIEBESKIND, JC
人类和实验动物的止痛反应具有显著的个体差异。这种变异性的遗传基础可以用选择性育种程序在啮齿动物身上进行实验研究。一个这样的程序被选为高(HA)和低(LA)游泳应激诱导镇痛(SSIA)在瑞士-韦氏小鼠的热板(56摄氏度)测试中。这些细胞系已经选择性地繁殖了25代以上，在阿片介导的SSIA(在38℃水中游泳3分钟)、吗啡镇痛(10 mg/kg，ip)和对kappa受体激动剂U-50,488H(30 mg/kg，ip)的镇痛方面表现出明显的差异。本研究采用孟德尔遗传分析方法，研究了HA和LA小鼠体内阿片类止痛药的遗传方式。我们报道，HA和LA小鼠对这些止痛操作的不同敏感性似乎是由一个或最多两个主要基因座决定的寡基因决定的。然而，与每种类型的止痛相关的基因座并不是共分离的，这表明已经确定了三种不同的寡聚效应。这些发现表明，止痛机制的基因决定可能只有简单的成分，因此可能适合于使用分子基因技术进行进一步的分析。
The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U-50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques.