The most prominent electrophysiological effect of ketamine is not sufficient to cause anesthesia.

NMDA receptor inhibition has been identified as a key functional property of numerous psychoactive drugs, anesthetics, and analgesics including alcohol, nitrous oxide, dextromethorphan, phencyclidine, and ketamine. This report investigates the role of NMDA receptor inhibition in ketamine-induced anesthesia by comparing the effects of systemic injections of ketamine and the highly selective NMDA receptor antagonist CGS 19755 on intracortical electrophysiological activity and behavior in rhesus macaques. Changes in cortical electrophysiology following sub-anesthetic doses of CGS 19755 resemble the "gamma-burst" activity caused by anesthetic doses of ketamine, while the behavioral effects of the two drugs differ considerably. This shows that while NMDA antagonism is sufficient to cause a key neural correlate of ketamine anesthesia, it is not sufficient on its own to cause anesthesia. These findings shed light on a previously unappreciated effect of systemic NMDA antagonism, and clarify the relationship between electrophysiological changes caused by ketamine and ketamine's anesthetic mechanisms.