N-Methyl d-Aspartate Receptor Antagonists Ketamine and MK-801 Induce Wake-Related Aberrant γ Oscillations in the Rat Neocortex
2007; Elsevier BV; Volume: 63; Issue: 8 Linguagem: Inglês
10.1016/j.biopsych.2007.10.006
ISSN1873-2402
Autores Tópico(s)Functional Brain Connectivity Studies
ResumoSingle 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?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%).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.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.
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