Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
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...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2007-12, Vol.318 (5856), p.1645-1647 |
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| creator | Behrens, M. Margarita Ali, Sameh S Dao, Diep N Lucero, Jacinta Shekhtman, Grigoriy Quick, Kevin L Dugan, Laura L |
| 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 γ-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. |
| doi_str_mv | 10.1126/science.1148045 |
| format | Article |
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Margarita ; Ali, Sameh S ; Dao, Diep N ; Lucero, Jacinta ; Shekhtman, Grigoriy ; Quick, Kevin L ; Dugan, Laura L</creator><creatorcontrib>Behrens, M. Margarita ; Ali, Sameh S ; Dao, Diep N ; Lucero, Jacinta ; Shekhtman, Grigoriy ; Quick, Kevin L ; Dugan, Laura L</creatorcontrib><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 γ-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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1148045</identifier><identifier>PMID: 18063801</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Acetophenones - pharmacology ; Adult and adolescent clinical studies ; Animals ; Biological and medical sciences ; Brain ; Brain - drug effects ; Brain - enzymology ; Brain - metabolism ; Brain research ; Cells, Cultured ; Enzyme Activation ; Enzyme Inhibitors - pharmacology ; Enzymes ; Fluorescence ; Genotype & phenotype ; Glutamate Decarboxylase - metabolism ; Interneurons ; Interneurons - drug effects ; Interneurons - enzymology ; Interneurons - metabolism ; Ketamine - pharmacology ; Male ; Medical sciences ; Membrane Glycoproteins - metabolism ; Mental disorders ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase 2 ; NADPH Oxidases - metabolism ; Neurons ; Oxidases ; Oxidation ; Oxidation-Reduction ; Parvalbumins - metabolism ; Phenotypes ; Psychology. 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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.</description><subject>Acetophenones - pharmacology</subject><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>Brain research</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzymes</subject><subject>Fluorescence</subject><subject>Genotype & phenotype</subject><subject>Glutamate Decarboxylase - metabolism</subject><subject>Interneurons</subject><subject>Interneurons - drug effects</subject><subject>Interneurons - enzymology</subject><subject>Interneurons - metabolism</subject><subject>Ketamine - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NADPH Oxidase 2</subject><subject>NADPH Oxidases - metabolism</subject><subject>Neurons</subject><subject>Oxidases</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Parvalbumins - metabolism</subject><subject>Phenotypes</subject><subject>Psychology. 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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 γ-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.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>18063801</pmid><doi>10.1126/science.1148045</doi><tpages>3</tpages></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2007-12, Vol.318 (5856), p.1645-1647 |
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| subjects | Acetophenones - pharmacology Adult and adolescent clinical studies Animals Biological and medical sciences Brain Brain - drug effects Brain - enzymology Brain - metabolism Brain research Cells, Cultured Enzyme Activation Enzyme Inhibitors - pharmacology Enzymes Fluorescence Genotype & phenotype Glutamate Decarboxylase - metabolism Interneurons Interneurons - drug effects Interneurons - enzymology Interneurons - metabolism Ketamine - pharmacology Male Medical sciences Membrane Glycoproteins - metabolism Mental disorders Mice Mice, Inbred C57BL NADPH Oxidase 2 NADPH Oxidases - metabolism Neurons Oxidases Oxidation Oxidation-Reduction Parvalbumins - metabolism Phenotypes Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Rodents Schizophrenia Superoxides Superoxides - metabolism Synaptic Transmission - drug effects Synaptosomes - metabolism |
| title | Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase |
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