Ketamine Impairs Brain by Releasing Superoxide

Ketamine Impairs Brain by Releasing Superoxide
THURSDAY, Dec. 6 (HealthDay News) -- Researchers say they havefigured out how the drug ketamine impairs the brain, a finding they claimcould lead to new treatments for schizophrenia.
The anesthetic/antidepressant triggers increased production of atoxic-free radical called superoxide and induces schizophrenia-likebehavior in drug users, but that action can be blocked, say researchers atthe University of California, San Diego, School of Medicine (UCSD).
The findings are published in the Dec. 7 issue of Science.
In this study with mice, the researchers discovered a link between aninflammatory enzyme complex (NADPH oxidase) and the dysfunction of certainbrain neurons exposed to ketamine. Normally, NADPH is found in white bloodcells circulating outside the brain, where it helps kill infections byproducing superoxide.
"Because of NADPH oxidase's protective role in fighting infection, itwas very surprising to find that the complex wears a second hat -- it isalso critical for modulating signaling in the brain," study first authorM. Margarita Behrens, of the geriatric medicine division at the UCSDSchool of Medicine, said in a prepared statement.
It was known that ketamine can impair inhibitory circuitry in the brainby blocking a receptor that controls neuron activity. But the UCSD teamfound that ketamine also greatly boosts the activity of NADPH, whichresults in further disruption of neuron signaling and impairment of braincircuitry involved in memory, attention and other important learningfunctions.
The researchers used ketamine to induce schizophrenia-like symptoms inmice and found that changes in the rodents' brains occurred in an areasimilar to where brain changes occur in people with schizophrenia.
When the researchers used an inhibitor to block the activity of NADPH,or a compound that wipes out superoxide, neurons in this brain area wereprotected.
"Our findings suggest that compounds that inhibit NADPH oxidase in thebrain, without totally blocking its protective function of killingbacteria, could provide future therapies for schizophrenia or otherdiseases in humans that exhibit similar changes in neural circuitry,"Behrens said.