Oxidative Stress Related to Drug-Induced Psychosis

Reduced NADPH oxidase may be a target for treating psychotomimetic effects of ketamine

MONDAY, Dec. 10 (HealthDay News) -- The schizophrenia-like syndrome caused by abuse of drugs such as ketamine may be due to increased oxidative stress mediated by increased activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, according to a report in the Dec. 7 issue of Science.

Noting that previous studies had found an increase in reactive oxygen species after treatment with N-methyl-D-aspartate (NMDA)-receptor antagonists such as ketamine, M. Margarita Behrens, Ph.D., and colleagues from the University of California San Diego treated mice with ketamine for two days. They then examined the activity of NADPH oxidase, which produces superoxide, in the brain.

The researchers found that the mice had increases in superoxide in several brain regions, which was blocked by treatment with an NADPH oxidase inhibitor or a superoxide dismutase mimetic.

"In summary, we hypothesize that NADPH oxidase may be a contributor to oxidative mechanisms involved not only in the psychotomimetic effects of NMDA-receptor antagonists, but also in schizophrenia and other processes involving increased oxidative stress in the brain," Behrens and colleagues conclude. "These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis."

Abstract
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