N-methyl d-aspartate receptor antagonists ketarnine 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 transientclisruption in NMDArfunction are unknown. Disorders of cognition-related coherences of gamma 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 gamma oscillations? Methods: Properties of spontaneously occurring gamma 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), apornorphine (<= 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 gamma oscillations in the neocortex. Substances that modulate doparninergic neurotransmission could also increase the gamma power but to a lesser degree. Conclusions: The present findings suggest that abnormal increased synchronization in ongoing gamma oscillations in cortical-related networks might cause dysfunctions of conscious integration, as seen in patients with schizophrenia.