PUBLICATION
A behavioral and molecular analysis of ketamine in zebrafish
- Authors
- Zakhary, S.M., Ayubcha, D., Ansari, F., Kamran, K., Karim, M., Leheste, J.R., Horowitz, J.M., and Torres, G.
- ID
- ZDB-PUB-100719-43
- Date
- 2011
- Source
- Synapse (New York, N.Y.) 65(2): 160-167 (Journal)
- Registered Authors
- Keywords
- Circling Behavior, Gill Movement, Hypoxia, Phox2b, Sirtuins
- MeSH Terms
-
- Analysis of Variance
- Animals
- Behavior, Animal/drug effects*
- Excitatory Amino Acid Antagonists/pharmacology*
- Exploratory Behavior/drug effects
- Gene Expression Regulation/drug effects*
- Homeodomain Proteins/metabolism
- Ketamine/pharmacology*
- Sirtuin 1/metabolism
- Stereotyped Behavior/drug effects
- Stress, Physiological/drug effects
- Time Factors
- Transcription Factors/metabolism
- Zebrafish/physiology
- PubMed
- 20623473 Full text @ Synapse
Citation
Zakhary, S.M., Ayubcha, D., Ansari, F., Kamran, K., Karim, M., Leheste, J.R., Horowitz, J.M., and Torres, G. (2011) A behavioral and molecular analysis of ketamine in zebrafish. Synapse (New York, N.Y.). 65(2):160-167.
Abstract
Ketamine exerts powerful anesthetic, psychotic and anti-depressant 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 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. Sub-anesthetic 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping