N-Methyl d-Aspartate Receptor Antagonists Ketamine and MK-801 Induce Wake-Related Aberrant γ Oscillations in the Rat Neocortex

Background Single subanesthetic doses of ketamine, a non-competitive NMDA receptor (NMDAr) antagonist, induce cognitive impairment, schizophreniform psychosis, hallucinations, and exacerbate schizophrenia symptoms. The neuronal mechanisms underlying transient disruption in NMDAr function are unknown. Disorders of cognition-related coherences of γ frequency (30–80 Hz) oscillations between cortical areas are a major functional abnormality in schizophrenic patients. Does a single subanesthetic dose of ketamine or MK-801 alter properties of cortical γ oscillations? Methods Properties of spontaneously occurring γ oscillations in the electrocorticogram of the neocortex of freely moving rats (n = 16) were measured before and after subcutaneous administration of a single dose of ketamine (≤ 10 mg/kg), MK-801 (≤ .16 mg/kg), d-amphetamine (≤ 1 mg/kg), apomorphine (≤ 1.6 mg/kg), or vehicle (sodium chloride, .9%). Results The present study gives the first evidence that ketamine and MK-801, both of which induce NMDAr-dependent functional disconnections, dose-dependently increase the power (200%–400%) of wake-related γ oscillations in the neocortex. Substances that modulate dopaminergic neurotransmission could also increase the γ power but to a lesser degree. Conclusions The present findings suggest that abnormal increased synchronization in ongoing γ oscillations in cortical-related networks might cause dysfunctions of conscious integration, as seen in patients with schizophrenia.