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

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 previous...

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Main Authors: Soichiro Ide, Hirofumi Kunitomo, Yuichi Iino, Kazutaka Ikeda
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.802701/full
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author Soichiro Ide
Hirofumi Kunitomo
Yuichi Iino
Kazutaka Ikeda
author_facet Soichiro Ide
Hirofumi Kunitomo
Yuichi Iino
Kazutaka Ikeda
author_sort Soichiro Ide
collection DOAJ
description 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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spelling doaj.art-d59a2f586e194e9fb3238f5ab2714d032022-12-21T18:13:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.802701802701Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17Soichiro Ide0Hirofumi Kunitomo1Yuichi Iino2Kazutaka Ikeda3Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Biological Sciences, Faculty of Science, Graduate School of Science, The University of Tokyo, Tokyo, JapanDepartment of Biological Sciences, Faculty of Science, Graduate School of Science, The University of Tokyo, Tokyo, JapanAddictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAddiction 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.802701/fullC. elegansmorphinepreferenceaddictionNPR-17
spellingShingle Soichiro Ide
Hirofumi Kunitomo
Yuichi Iino
Kazutaka Ikeda
Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
Frontiers in Pharmacology
C. elegans
morphine
preference
addiction
NPR-17
title Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
title_full Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
title_fullStr Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
title_full_unstemmed Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
title_short Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
title_sort caenorhabditis elegans exhibits morphine addiction like behavior via the opioid like receptor npr 17
topic C. elegans
morphine
preference
addiction
NPR-17
url https://www.frontiersin.org/articles/10.3389/fphar.2021.802701/full
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