Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence in rats. The drug rapidly penetrates the brain, reaching peak concentrations within 15 minutes after administration. Ketamine also produces marked hyperlocomotion and deficits in prepulse inhibition of the acoustic startle reaction, a measure of sensorimotor gating. The maximum levels of EEG change correlate with the kinetics of ketamine, and the effects are most pronounced at 10-15 minutes after administration of 30 mg/kg.
A single dose of ketamine (0.54 mg/kg infused over 30 minutes) rapidly alters brain electrical activity in healthy volunteers, producing a decrease in prefrontal theta cordance—a QEEG measure linked to cerebral blood flow—and an increase in central region theta cordance within 10 to 30 minutes. These changes resemble those seen after one week of treatment with standard antidepressants in people who respond to them, but occur much faster. The prefrontal theta cordance reduction correlated with ketamine and norketamine blood levels at 10 minutes. The findings suggest that theta cordance reduction could serve as a marker and predictor of ketamine's rapid antidepressant effect, a hypothesis warranting testing in depressed patients.