Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Science December 6, 2007 M. Margarita Behrens, Sameh S. Ali, Diep N. Dao et al. 590 citations
Repeated exposure to the anesthetic ketamine, which blocks NMDA receptors, causes a lasting increase in superoxide in the brain by activating NADPH oxidase in neurons. This increase in superoxide leads to dysfunction of fast-spiking inhibitory interneurons in the prefrontal cortex, specifically reducing their expression of parvalbumin and the GABA-producing enzyme GAD67—changes that mirror those seen in schizophrenia. Lowering superoxide production prevented these effects on inhibitory interneurons. The findings suggest that targeting NADPH oxidase could offer a new approach for treating ketamine-induced psychosis.