N-methyl d-aspartate receptor antagonists ketamine and MK-801 induce wake-related aberrant gamma oscillations in the rat neocortex

Biol Psychiatry. 2008 Apr 15;63(8):730-5. doi: 10.1016/j.biopsych.2007.10.006. Epub 2007 Nov 26.


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 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 (< or = 10 mg/kg), MK-801 (< or = .16 mg/kg), d-amphetamine (< or = 1 mg/kg), apomorphine (< or = 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 dopaminergic 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Arousal / drug effects
  • Cortical Synchronization
  • Dextroamphetamine / pharmacology
  • Dizocilpine Maleate / pharmacology*
  • Dopamine Agonists / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Electroencephalography / drug effects*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Injections, Subcutaneous
  • Ketamine / pharmacology*
  • Male
  • Neocortex / drug effects*
  • Nerve Net / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Synaptic Transmission / drug effects
  • Wakefulness / drug effects


  • Dopamine Agonists
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Dizocilpine Maleate
  • Apomorphine
  • Dextroamphetamine