A behavioral and molecular analysis of ketamine in zebrafish.
Sherry M Zakhary, Diana Ayubcha, Farah Ansari, Kiran Kamran, Mehwish Karim, Joerg R Leheste, Judith M Horowitz, German Torres
Synapse February 2011 DOI: 10.1002/syn.20830 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Zebrafish |
| Intervention | Ketamine |
| Dose | subanesthetic doses |
| Topics | Esketamine Ketamine |
| Key findings | Subanesthetic ketamine doses caused abnormal behaviors in zebrafish analogous to transient psychosis in humans and rodents. The transcription factor Phox2b is a molecular substrate for ketamine's actions, particularly during hypoxic stress, and SIRT1 is also affected by hypoxia crises. |
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 critical sensory circuits that monitor breathing behavior.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 19
- Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2012
- Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research. Behavioural Brain Research 2013
- Behavioral effects of MDMA (‘ecstasy’) on adult zebrafish Behavioural Pharmacology April 8, 2011
- Exposure to ayahuasca induces developmental and behavioral alterations on early life stages of zebrafish Chemico-Biological Interactions August 4, 2018
- Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models Zebrafish March 22, 2016
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Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase Science December 6, 2007
- Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression The World Journal of Biological Psychiatry May 12, 2008
- Anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. Neuroscience June 30, 2009
and 2 more in the library