Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 7 December 2007:
Vol. 318. no. 5856, pp. 1645 - 1647
DOI: 10.1126/science.1148045
Prev | Table of Contents | Next

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Depleting Rac1 in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function.
M. Haruta, R. A. Bush, S. Kjellstrom, C. Vijayasarathy, Y. Zeng, Y.-Z. Le, and P. A. Sieving (2009)
PNAS 106, 9397-9402
   Abstract »    Full Text »    PDF »
A Loss of Parvalbumin-Containing Interneurons Is Associated with Diminished Oscillatory Activity in an Animal Model of Schizophrenia.
D. J. Lodge, M. M. Behrens, and A. A. Grace (2009)
J. Neurosci. 29, 2344-2354
   Abstract »    Full Text »    PDF »
Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia.
M. M. Behrens, S. S. Ali, and L. L. Dugan (2008)
J. Neurosci. 28, 13957-13966
   Abstract »    Full Text »    PDF »
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:

Read all E-Letters

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

To Advertise     Find Products

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