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Science 7 December 2007:
Vol. 318. no. 5856, pp. 1645 - 1647
DOI: 10.1126/science.1148045
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Reports

Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase

M. Margarita Behrens,* Sameh S. Ali, Diep N. Dao, Jacinta Lucero, Grigoriy Shekhtman, Kevin L. Quick, Laura L. Dugan*

Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-D-aspartate–receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the {gamma}-aminobutyric acid–producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.

Department of Medicine, Division of Geriatric Medicine, University of California San Diego, La Jolla, CA 92093–0746, USA.

* To whom correspondence should be addressed. E-mail: mbehrens{at}ucsd.edu (M.M.B.); ladugan{at}ucsd.edu (L.L.D.)

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Region-Specific Changes in Gamma and Beta2 Rhythms in NMDA Receptor Dysfunction Models of Schizophrenia.
A. K. Roopun, M. O. Cunningham, C. Racca, K. Alter, R. D. Traub, and M. A. Whittington (2008)
Schizophr Bull 34, 962-973
   Abstract »    Full Text »    PDF »
GABA Neurons and the Mechanisms of Network Oscillations: Implications for Understanding Cortical Dysfunction in Schizophrenia.
G. Gonzalez-Burgos and D. A. Lewis (2008)
Schizophr Bull 34, 944-961
   Abstract »    Full Text »    PDF »
Prolonged Exposure to NMDAR Antagonist Suppresses Inhibitory Synaptic Transmission in Prefrontal Cortex.
Y. Zhang, M. M. Behrens, and J. E. Lisman (2008)
J Neurophysiol 100, 959-965
   Abstract »    Full Text »    PDF »

E-Letters:

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NADPH Oxidase and Ionic Movements
Heikki Savolainen
Science Online, 24 Jan 2008 [Full text]

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Science. ISSN 0036-8075 (print), 1095-9203 (online)