An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice
An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice
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DOI：
10.1016/0361-9230(95)02092-6
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发表时间：
1996-01-01
影响因子：
3.8
通讯作者：
Inturrisi, CE
中科院分区：
文献类型：
--
作者：
Kest, B;Lee, CE;Inturrisi, CE
来自几个实验室的药理学数据支持δ阿片受体在吗啡镇痛、耐受和身体依赖中的调节作用。我们研究了δ阿片受体在这些过程中的作用，在小鼠体内使用反义策略。与未处理或盐水处理的小鼠相比，脑室内施用靶向克隆的δ阿片受体（DOR-1）的mRNA的20聚体反义或错配对照寡脱氧核苷酸（ODN）3天不影响基线伤害感受阈值或吗啡镇痛。然而，剂量-反应研究表明，慢性吗啡给药3天后，吗啡耐受的诱导在反义而非错配中被阻断，ODN或盐水处理的小鼠。反义ODN治疗也阻断了急性吗啡依赖的发展，而盐水或错配ODN治疗的小鼠没有提供类似的保护。这项研究证明了克隆的DOR-1在吗啡耐受和依赖中的相关性，并为使用这种新方法调节δ阿片受体的作用提供了新的证据。
Pharmacological data from several laboratories support a modulatory role for the delta opioid receptor in morphine analgesia, tolerance, and physical dependence. We examined the role of the delta opioid receptor in these processes using an in vivo antisense strategy in mice. Intracerebroventricular administration of a 20mer antisense or a mismatch control oligodeoxynucleotide (ODN) targeting the mRNA of the cloned delta opioid receptor (DOR-1) for 3 days did not affect baseline nociceptive thresholds or morphine analgesia compared to untreated or saline-treated mice, However, dose-response studies indicate that the induction of morphine tolerance following 3 days of chronic morphine administration was blocked in antisense but not mismatch ODN or saline-treated mice. Antisense ODN treatment also blocked the development of acute morphine dependence, whereas similar protection was not afforded to mice treated with saline or mismatch ODN. This study demonstrates the relevance of the cloned DOR-1 in morphine tolerance and dependence and provides new evidence for a modulatory role of the delta opioid receptor using this novel approach.