A behavioral and molecular analysis of ketamine in zebrafish.

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Sherry M ZakharyGerman Torres

Abstract

Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N-methyl-D-aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Subanesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects crit...Continue Reading

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Citations

Jul 26, 2013·ACS Chemical Neuroscience·Nikhil NeelkantanAllan V Kalueff
Apr 28, 2011·Behavioural Pharmacology·Adam StewartAllan V Kalueff
Nov 30, 2013·Neurotoxicology and Teratology·Luís M FélixAna M Coimbra
Sep 24, 2014·Aquatic Toxicology·Adam Michael StewartAllan V Kalueff
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Oct 27, 2011·Reproductive Toxicology·Jyotshnabala KanungoMerle G Paule
Jun 21, 2011·Neurotoxicology and Teratology·Russell RiehlAllan V Kalueff
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Nov 3, 2011·Journal of Applied Toxicology : JAT·Jyotshna KanungoMerle G Paule
Mar 6, 2012·Brain Research·Lee David EllisKelly Howard Soanes
Apr 1, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Anderson Manoel Herculano, Caio Maximino
Jul 19, 2015·Behavioural Brain Research·Eduardo Geraldo De CamposBruno Spinosa De Martinis
Aug 21, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Adam Michael StewartAllan V Kalueff
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Jan 19, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Evan J KyzarAllan V Kalueff
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Dec 10, 2016·Psychopharmacology·Luís M FélixAna M Valentim
Jan 25, 2018·Pathogens and Disease·German TorresJoerg R Leheste
Oct 27, 2020·Frontiers in Psychiatry·Veronika LangovaJiri Horacek
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Aug 14, 2018·Neuroscience Letters·Paula MichelottiDenis B Rosemberg
Oct 3, 2021·Neurotoxicology and Teratology·Debora Dreher NabingerCarla Denise Bonan

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