Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17.

Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17.
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DOI:
10.3389/fphar.2021.802701
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发表时间:
2021
影响因子:
5.6
通讯作者:
Ikeda K
Ikeda K
中科院分区:
医学2区
文献类型:
--
作者:
Ide S;Kunitomo H;Iino Y;Ikeda K

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成瘾已经成为世界范围内的一个严重的社会问题,有效的治疗方法很少。线虫线虫是研究神经生物学疾病状态的优秀无脊椎动物模型。据报道,线虫对以前与成瘾药物配对的线索产生了偏好,类似于在啮齿动物身上发现的条件反射。此外,最近的几项研究发现并报告了线虫中存在类阿片系统。然而,尚不清楚的是,线虫是否对阿片类药物表现出类似于吗啡的上瘾行为。在本研究中,我们利用条件性化学感觉线索偏好(CCP)测试发现线虫对吗啡表现出剂量依赖的偏好。这种偏爱被阿片受体拮抗剂纳洛酮联合治疗所阻断。线虫也表现出对纳洛酮催促戒断慢性吗啡暴露的厌恶。在缺乏阿片样受体NPR-17的蠕虫中,吗啡诱导的CCP的表达和吗啡的戒断被取消。多巴胺缺乏突变体(CAT-2(E1112))蠕虫也不表现出吗啡诱导的CCP。这些结果表明线虫体内存在阿片系统的成瘾功能,这可能是一种有用的阿片成瘾模型。
Addiction has become a profound societal problem worldwide, and few effective treatments are available. The nematode Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study neurobiological disease states. C. elegans reportedly developed a preference for cues that had previously been paired with addictive drugs, similar to place conditioning findings in rodents. Moreover, several recent studies discovered and reported the existence of an opioid-like system in C. elegans. Still unclear, however, is whether C. elegans exhibits addictive-like behaviors for opioids, such as morphine. In the present study, we found that C. elegans exhibited dose-dependent preference for morphine using the conditioned chemosensory-cue preference (CCP) test. This preference was blocked by co-treatment with the opioid receptor antagonist naloxone. C. elegans also exhibited aversion to naloxone-precipitated withdrawal from chronic morphine exposure. The expression of morphine-induced CCP and morphine withdrawal were abolished in worms that lacked the opioid-like receptor NPR-17. Dopamine-deficient mutant (cat-2 (e1112)) worms also did not exhibit morphine-induced CCP. These results indicate that the addictive function of the opioid system exists in C. elegans, which may serve as a useful model of opioid addiction.
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