Assessment of delta opioid antinociception and receptor mRNA levels in mouse after chronic naltrexone treatment.
Assessment of delta opioid antinociception and receptor mRNA levels in mouse after chronic naltrexone treatment.
复制标题
慢性纳曲酮治疗后小鼠 Delta 阿片类镇痛作用和受体 mRNA 水平的评估。
DOI：
10.1016/0006-8993(95)00615-w
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Inturrisi,CE
中科院分区：
文献类型：
--
作者：
Jenab,S;Kest,B;Inturrisi,CE
在长期接受纳曲酮治疗的小鼠中测量了 δ 阿片受体 (DOR) 激动剂 [D-Ala2]Deltorphin II 的镇痛功效和 DOR mRNA 水平。 [D-Ala2]Deltorphin II 的 ED50 测定，使用甩尾试验对接受纳曲酮治疗 7 天，随后 24 小时不使用纳曲酮期（第 8 天）的小鼠进行，结果显示抗伤害效力增加了 7.7 倍，表明功能性超敏性。利用显微解剖技术，然后对小鼠中枢神经系统的 RNA 提取物进行定量溶液杂交测量，揭示了 DOR mRNA 的水平范围从尾壳核中的 2.8 pg/μg RNA 到小脑中的 0.3 pg/μg RNA。然而，尽管 DOR 敏感性功能性增加，但纳曲酮治疗组和对照小鼠的选定脑区和脊髓中的 DOR mRNA 水平没有差异。在纳曲酮治疗和对照小鼠中较短的治疗间隔（1、6和12小时以及2和7天）后对全脑和选定CNS区域的DOR mRNA水平的评估显示了相似的结果模式。纳曲酮治疗 7 天后，对小鼠全脑 RNA 提取物进行 Northern 印迹分析，未显示 DOR 转录物大小有任何变化。这些数据表明，DOR mRNA 水平在长期纳曲酮治疗期间和之后没有改变，因此与阿片类药物诱导的 DOR 上调或 DOR 功能超敏感性无关。
The antinociceptive potency of the delta opioid receptor (DOR) agonist [D-Ala2]Deltorphin II and the levels of DOR mRNA were measured in mice chronically treated with naltrexone. ED50determinations for [D-Ala2]Deltorphin II, using the tail-flick test with mice that had been treated with naltrexone for 7 days followed by a 24 h naltrexone free period (study day 8), revealed a 7.7-fold increase in antinociceptive potency, indicating functional supersensitivity. Utilization of a micro-dissection technique followed by quantitative solution hybridization measurements of RNA extracts from mouse CNS revealed levels of DOR mRNA ranging from 2.8 pg/μg RNA in the caudate-putamen to 0.3 pg/μg RNA in cerebellum. However, despite the functional increase in DOR sensitivity, the DOR mRNA levels in selected brain areas and spinal cord of naltrexone-treated and control mice did not differ. Assessment of DOR mRNA levels in whole brain and selected CNS regions after shorter treatment intervals (1, 6 and 12 h and 2 and 7 days) in naltrexone-treated and control mice revealed a similar pattern of results. Northern blot analysis of mouse whole brain RNA extracts after 7 days of naltrexone treatment did not show any alteration in the size of the DOR transcript. These data demonstrate that DOR mRNA levels are not altered during and after chronic naltrexone treatment and therefore are not associated with opioid-induced DOR up-regulation or DOR functional supersensitivity.