ToxSci Advance Access published online on March 31, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj180
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1 Chef de Clinique Scientifique, Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland
* To whom correspondence should be addressed. Ketamine, a non-competitive antagonist of the N-methyl-D-aspartate type of glutamate receptors, was reported to induce neuronal cell death when administered to produce anaesthesia in young rodents and monkeys. Subanesthetic doses of ketamine, as adjuvant to postoperative sedation and pain control, are also frequently administered to young children. However the effects of these low concentrations of ketamine on neuronal development remain unknown. The present study was designed to evaluate the effects of increasing concentrations (0.01 - 40 µg/ml) and durations (1-96 hours) of ketamine exposure on the differentiation and survival of immature GABAergic interneurons in culture. In line with previous studies (Scallet et al., 2004), we found that a 1-hour long exposure to ketamine at concentrations
Received February 14, 2006
Accepted March 27, 2006
Neurotoxicology
Effect of Ketamine on Dendritic Arbour Development and Survival of Immature GABAergic Neurons in vitro
Laszlo Vutskits M.D., Ph.D. 1 *,
Eduardo Gascon M.D. 2,
Edomer Tassonyi M.D. 3,
and
Jozsef Z. Kiss M.D. 4
2 Research resident, Department of Neuroscience, University of Geneva Medical School, Geneva, Switzerland
3 Professor, Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland
4 Professor, Department of Neuroscience, University of Geneva Medical School, Geneva, Switzerland
Laszlo Vutskits, E-mail: laszlo.vutskits{at}hcuge.ch
Abstract 
10 µg/ml was sufficient to trigger cell death. At lower concentrations of ketamine, cell loss was only observed when this drug was chronically (> 48 hours) present in the culture medium. Most importantly, we found that a single episode of 4-hour-long treatment with 5 µg/ml ketamine induced long-term alterations in dendritic growth, including a significant (p < 0.05) reduction in total dendritic length and in the number of branching points compared to control groups. Finally, long-term exposure (>24 hours) of neurons to ketamine at concentrations as low as 0.01 µg/ml also severely impaired dendritic arbour development. These results suggest that, in addition to its dose-dependent ability to induce cell death, even very low concentrations of ketamine could interfere with dendritic arbour development of immature GABAergic neurons and thus could potentially interfere with the development neural networks.
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