Publication Date:
2007-12-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrens, M Margarita -- Ali, Sameh S -- Dao, Diep N -- Lucero, Jacinta -- Shekhtman, Grigoriy -- Quick, Kevin L -- Dugan, Laura L -- New York, N.Y. -- Science. 2007 Dec 7;318(5856):1645-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Geriatric Medicine, University of California San Diego, La Jolla, CA 92093-0746, USA. mbehrens@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18063801" target="_blank"〉PubMed〈/a〉
Keywords:
Acetophenones/pharmacology
;
Animals
;
Brain/*drug effects/enzymology/metabolism
;
Cells, Cultured
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Glutamate Decarboxylase/metabolism
;
Interneurons/*drug effects/enzymology/*metabolism
;
Ketamine/*pharmacology
;
Male
;
Membrane Glycoproteins/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
NADPH Oxidase/*metabolism
;
Oxidation-Reduction
;
Parvalbumins/metabolism
;
Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
;
Superoxides/*metabolism
;
Synaptic Transmission/drug effects
;
Synaptosomes/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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