Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish
A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A serie...
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| creator | Khor, Beng-Siang Jamil, Mohd Fadzly Amar Adenan, Mohamad Ilham Shu-Chien, Alexander Chong |
| description | A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. |
| doi_str_mv | 10.1371/journal.pone.0028340 |
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Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0028340</identifier><identifier>PMID: 22205946</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Addicts ; Analysis ; Animal behavior ; Animals ; Anxiety ; Anxiety - drug therapy ; Attenuation ; Behavior, Animal - drug effects ; Biology ; Brain ; Conditioning (Psychology) - drug effects ; Corticotropin-releasing hormone ; Cortisol ; Danio rerio ; Diving ; Drug abuse ; Drug addiction ; Enkephalins - genetics ; Exploratory behavior ; Female ; Gene expression ; Gene Expression Regulation - drug effects ; Genetic aspects ; Glucocorticoids ; Hydrocortisone - biosynthesis ; Hydrocortisone - metabolism ; Leaves ; Male ; Medicine ; Mitragyna speciosa ; Morphine ; Morphine - pharmacology ; Neurophysiology ; Neurosciences ; Pharmaceuticals ; Prodynorphin ; Protein Precursors - genetics ; Receptors ; Receptors, Corticotropin-Releasing Hormone - genetics ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Science ; Secologanin Tryptamine Alkaloids - pharmacology ; Secologanin Tryptamine Alkaloids - therapeutic use ; Spatial Behavior - drug effects ; Stress ; Stresses ; Substance Withdrawal Syndrome - drug therapy ; Substance Withdrawal Syndrome - genetics ; Substance Withdrawal Syndrome - metabolism ; Substance Withdrawal Syndrome - psychology ; Swimming ; Swimming behavior ; Withdrawal ; Zebrafish</subject><ispartof>PloS one, 2011-12, Vol.6 (12), p.e28340</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Khor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Khor et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-af26f07a386cc3c8fe06e3fd35a4950eab3102d77d3b8a9d111a6b623aa43c473</citedby><cites>FETCH-LOGICAL-c691t-af26f07a386cc3c8fe06e3fd35a4950eab3102d77d3b8a9d111a6b623aa43c473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244390/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244390/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22205946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ramchandran, Ramani</contributor><creatorcontrib>Khor, Beng-Siang</creatorcontrib><creatorcontrib>Jamil, Mohd Fadzly Amar</creatorcontrib><creatorcontrib>Adenan, Mohamad Ilham</creatorcontrib><creatorcontrib>Shu-Chien, Alexander Chong</creatorcontrib><title>Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.</description><subject>Addicts</subject><subject>Analysis</subject><subject>Animal behavior</subject><subject>Animals</subject><subject>Anxiety</subject><subject>Anxiety - drug therapy</subject><subject>Attenuation</subject><subject>Behavior, Animal - drug effects</subject><subject>Biology</subject><subject>Brain</subject><subject>Conditioning (Psychology) - drug effects</subject><subject>Corticotropin-releasing hormone</subject><subject>Cortisol</subject><subject>Danio rerio</subject><subject>Diving</subject><subject>Drug abuse</subject><subject>Drug addiction</subject><subject>Enkephalins - genetics</subject><subject>Exploratory behavior</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - 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Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22205946</pmid><doi>10.1371/journal.pone.0028340</doi><tpages>e28340</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-12, Vol.6 (12), p.e28340 |
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| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Addicts Analysis Animal behavior Animals Anxiety Anxiety - drug therapy Attenuation Behavior, Animal - drug effects Biology Brain Conditioning (Psychology) - drug effects Corticotropin-releasing hormone Cortisol Danio rerio Diving Drug abuse Drug addiction Enkephalins - genetics Exploratory behavior Female Gene expression Gene Expression Regulation - drug effects Genetic aspects Glucocorticoids Hydrocortisone - biosynthesis Hydrocortisone - metabolism Leaves Male Medicine Mitragyna speciosa Morphine Morphine - pharmacology Neurophysiology Neurosciences Pharmaceuticals Prodynorphin Protein Precursors - genetics Receptors Receptors, Corticotropin-Releasing Hormone - genetics RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Science Secologanin Tryptamine Alkaloids - pharmacology Secologanin Tryptamine Alkaloids - therapeutic use Spatial Behavior - drug effects Stress Stresses Substance Withdrawal Syndrome - drug therapy Substance Withdrawal Syndrome - genetics Substance Withdrawal Syndrome - metabolism Substance Withdrawal Syndrome - psychology Swimming Swimming behavior Withdrawal Zebrafish |
| title | Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-10T02%3A55%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitragynine%20attenuates%20withdrawal%20syndrome%20in%20morphine-withdrawn%20zebrafish&rft.jtitle=PloS%20one&rft.au=Khor,%20Beng-Siang&rft.date=2011-12-21&rft.volume=6&rft.issue=12&rft.spage=e28340&rft.pages=e28340-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0028340&rft_dat=%3Cgale_plos_%3EA476858253%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312164345&rft_id=info:pmid/22205946&rft_galeid=A476858253&rft_doaj_id=oai_doaj_org_article_70e58699538c47ba9bcedfdd5448a181&rfr_iscdi=true |