μ opiate receptor gene dose effects on different morphine actions:: Evidence for differential in vivo μ receptor reserve
μ opiate receptor gene dose effects on different morphine actions:: Evidence for differential in vivo μ receptor reserve
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DOI：
10.1016/s0893-133x(00)00252-9
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发表时间：
2001-07-01
影响因子：
7.6
通讯作者：
Uhl, GR
中科院分区：
文献类型：
--
作者：
Sora, I;Elmer, G;Uhl, GR
没有μ阿片受体的纯合子转基因敲除小鼠缺乏吗啡诱导的抗伤害感受、运动、耐受性、身体依赖性和奖赏。因此，μ受体似乎在这些吗啡作用中起中心作用。在不同的人和不同的动物品系中发现了不同水平的mu受体表达。体外研究表明，一些吗啡反应持续灭活后，多达90%的初始mu受体补体，而其他人被减弱后，灭活少得多的受体。因此，不同水平的mu受体储备可能存在于体内不同的mu表达神经元群体中。杂合mu受体敲除小鼠表达野生型mu受体水平的一半。在这些小鼠中对吗啡作用的测试揭示了在介导不同阿片作用的脑回路中不同μ受体储备的证据。与野生型小鼠相比，杂合子表现出减弱的运动，减少吗啡自我管理，完整的耐受性，吗啡致死剂量/效应关系的快速变化，以及对位置偏好的可变影响。他们表现出完全的身体依赖性，通过吗啡给药5天后纳洛酮催促戒断来衡量。神经适应性变化的网站以外的mu受体可能参与其中的一些结果。然而，这些数据文件的μ受体表达水平的个体差异可能会对不同的阿片类药物的作用产生重大影响。他们支持这样的观点，即功能性μ受体储备在介导阿片类药物不同特性的不同神经元群体中存在差异。[Neuropsychopharmacology 25：41-54，2001]（C）2001年美国神经精神药理学学院。出版社：Elsevier Science Inc.
Homozygous transgenic knockout mice without mu -opioid receptors lack morphine-induced antinociception, locomotion, tolerance, physical dependence, and reward. mu receptors thus appear to play central roles in these morphine actions. Different levels of mu receptor expression are found in different humans and in different animal strains. In vitro studies indicate that some morphine responses persist after inactivation of as many as 90% of the initial mu receptor complement, while others are attenuated after inactivating many fewer receptors. Varying levels of mu receptor reserve could thus exist in different mu -expressing neuronal populations in vivo. Heterozygous mu receptor knockout mice express half of wild-type mu receptor levels. Tests of morphine actions in these mice reveal evidence for differing mu receptor reserves in brain circuits that mediate distinct opiate effects. Heterozygotes display attenuated locomotion, reduced morphine self-administration, intact tolerance, rightward shifts in morphine lethality dose/effect relationships, and variable effects on place preference compared to wild-type mice. They demonstrate full physical dependence, as measured by naloxone-precipitated abstinence following five days of morphine administration. Neuroadaptive changes in sites other than mu receptors could be involved in some of these results. Nevertheless, these data document substantial influences that individual differences in levels of mu receptor expression could exert on distinct opiate drug effects. They support the idea that functional mu receptor reserve differs among the diverse neuronal populations that mediate distinct properties of opiate drugs. [Neuropsychopharmacology 25:41-54, 2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.