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
Science December 6, 2007 DOI: 10.1126/science.1148045 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Nadph oxidase Parvalbumin Inhibitory postsynaptic potential Superoxide Nmda receptor Gabaa receptor Glutamate receptor Oxidase test Pharmacology Biochemistry Enzyme |
| Citations | 590 |
| Key findings | Ketamine-induced superoxide production via NADPH oxidase in neurons causes dysfunction of cortical fast-spiking inhibitory interneurons, which can be prevented by reducing superoxide. |
Abstract
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.