A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study w...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:7cf46bf568c24f43acb9b2b7d47b620b2021-11-22T07:29:39ZA Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure1663-981210.3389/fphar.2021.770319https://doaj.org/article/7cf46bf568c24f43acb9b2b7d47b620b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.770319/fullhttps://doaj.org/toc/1663-9812Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure. After an initial testing at 20 and 40 mg/L for 48 h, the later METH concentration was selected for developing the model and the effects on the brain monoaminergic profile, locomotor, anxiety-like and social behaviors as well as on the expression of key genes of the catecholaminergic system were determined. A concentration- and time-dependent decrease in the brain levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) was found in METH-exposed fish. A significant hyperactivity was found during the first hour of exposure, followed 3 h after by a positive geotaxis and negative scototaxis in the novel tank and in the light/dark paradigm, respectively. Moreover, the behavioral phenotype in the treated fish was consistent with social isolation. At transcriptional level, th1 and slc18a2 (vmat2) exhibited a significant increase after 3 h of exposure, whereas the expression of gfap, a marker of astroglial response to neuronal injury, was strongly increased after 48 h exposure. However, no evidences of oxidative stress were found in the brain of the treated fish. Altogether, this study demonstrates the suitability of the adult zebrafish as a model of METH-induced neurotoxicity and provides more information about the biochemical and behavioral consequences of METH abuse.Juliette BedrossiantzMarina BellotPol Dominguez-GarcíaMelissa FariaEva PratsCristian Gómez-CanelaRaul López-ArnauElena EscubedoDemetrio RaldúaFrontiers Media S.A.articlemethamphetamine neurotoxicityzebrafish modelbehaviorneurochemicalsgene expressionTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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DOAJ |
| collection |
DOAJ |
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| topic |
methamphetamine neurotoxicity zebrafish model behavior neurochemicals gene expression Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
methamphetamine neurotoxicity zebrafish model behavior neurochemicals gene expression Therapeutics. Pharmacology RM1-950 Juliette Bedrossiantz Marina Bellot Pol Dominguez-García Melissa Faria Eva Prats Cristian Gómez-Canela Raul López-Arnau Elena Escubedo Demetrio Raldúa A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| description |
Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure. After an initial testing at 20 and 40 mg/L for 48 h, the later METH concentration was selected for developing the model and the effects on the brain monoaminergic profile, locomotor, anxiety-like and social behaviors as well as on the expression of key genes of the catecholaminergic system were determined. A concentration- and time-dependent decrease in the brain levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) was found in METH-exposed fish. A significant hyperactivity was found during the first hour of exposure, followed 3 h after by a positive geotaxis and negative scototaxis in the novel tank and in the light/dark paradigm, respectively. Moreover, the behavioral phenotype in the treated fish was consistent with social isolation. At transcriptional level, th1 and slc18a2 (vmat2) exhibited a significant increase after 3 h of exposure, whereas the expression of gfap, a marker of astroglial response to neuronal injury, was strongly increased after 48 h exposure. However, no evidences of oxidative stress were found in the brain of the treated fish. Altogether, this study demonstrates the suitability of the adult zebrafish as a model of METH-induced neurotoxicity and provides more information about the biochemical and behavioral consequences of METH abuse. |
| format |
article |
| author |
Juliette Bedrossiantz Marina Bellot Pol Dominguez-García Melissa Faria Eva Prats Cristian Gómez-Canela Raul López-Arnau Elena Escubedo Demetrio Raldúa |
| author_facet |
Juliette Bedrossiantz Marina Bellot Pol Dominguez-García Melissa Faria Eva Prats Cristian Gómez-Canela Raul López-Arnau Elena Escubedo Demetrio Raldúa |
| author_sort |
Juliette Bedrossiantz |
| title |
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| title_short |
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| title_full |
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| title_fullStr |
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| title_full_unstemmed |
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure |
| title_sort |
zebrafish model of neurotoxicity by binge-like methamphetamine exposure |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/7cf46bf568c24f43acb9b2b7d47b620b |
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