N-methyl d-aspartate receptor antagonists ketamine and MK-801 induce wake-related aberrant gamma 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 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.
Pinault
Didier
D
INSERM U666, Physiopathologie Clinique et Expérimentale de la Schizophrénie, Faculté de Médecine, Strasbourg, France. pinault@neurochem.u-strasbg.fr
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects; D003344:Cortical Synchronization; D003913:Dextroamphetamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D019579:Neocortex / Q000187:drug effects*; D009415:Nerve Net / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D001058:Apomorphine; D003913:Dextroamphetamine