Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase

被引：445

作者：

Behrens, M. Margarita ^{[1
]}

Ali, Sameh S. ^{[1
]}

Dao, Diep N. ^{[1
]}

Lucero, Jacinta ^{[1
]}

Shekhtman, Grigoriy ^{[1
]}

Quick, Kevin L. ^{[1
]}

Dugan, Laura L. ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Med, Div Geriatr Med, La Jolla, CA 92093 USA

来源：

SCIENCE | 2007年 / 318卷 / 5856期

关键词：

D O I：

10.1126/science.1148045

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1645 / 1647

页数：3

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