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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward
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Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward

机译：阿片类镇痛需要中枢5-羟色胺神经元，但吗啡耐受或吗啡奖励并非如此

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摘要

Opioids remain the most effective analgesics despite their potential adverse effects such as tolerance and addiction. Mechanisms underlying these opiate-mediated processes remain the subject of much debate. Here we describe opioid-induced behaviors of Lm×1b conditional knockout mice [Lm×1b~(f/f/P)). which lack central serotonergic neurons, and we report that opioid analgesia is differentially dependent on the central serotonergic system. Analgesia induced by a κ opioid receptor agonist administered at the su-praspinal level was abolished in Lm×1b~(f/f/P) mice compared with their wild-type littermates. Furthermore, compared with their wild-type littermates Lm×1b~(f/f/P) mice exhibited significantly reduced analgesic effects of μ and δ opioid receptor agonists at both spinal and supraspinal sites. In contrast to the attenuation in opioid analgesia, Lm×1b~(f/f/P) mice developed tolerance to morphine analgesia and displayed normal morphine reward behavior as measured by conditioned place preference. Our results provide genetic evidence supporting the view that the central serotonergic system is a key component of supraspinal pain modulatory circuitry mediating opioid analgesia. Furthermore, our data suggest that the mechanisms of morphine tolerance and morphine reward are independent of the central serotonergic system.
机译：阿片类药物尽管有潜在的不良反应，例如耐受性和成瘾性，但仍然是最有效的镇痛药。这些阿片剂介导的过程的基础机制仍然是许多争论的主题。在这里，我们描述了阿片样物质诱导的Lm×1b条件性基因敲除小鼠的行为[Lm×1b〜（f / f / P））。缺乏中枢5-羟色胺能神经元，并且我们报告说，阿片类镇痛差异性地取决于中枢5-羟色胺能系统。与野生型同窝仔猪相比，Lm×1b〜（f / f / P）小鼠取消了以su-praspinal水平施用κ阿片受体激动剂引起的镇痛作用。此外，与野生型同窝小鼠相比，Lm×1b〜（f / f / P）小鼠在脊髓和脊髓上位均表现出μ和δ阿片受体激动剂的镇痛作用明显降低。与阿片类镇痛作用减弱相反，Lm×1b〜（f / f / P）小鼠对吗啡镇痛具有耐受性，并通过条件性位置偏爱测量显示出正常的吗啡奖励行为。我们的结果提供了遗传学证据，支持以下观点：中央血清素能系统是介导阿片类镇痛的脊髓上痛调节电路的关键组成部分。此外，我们的数据表明吗啡耐受和吗啡奖励的机制独立于中央血清素能系统。

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