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Toward an Explanation of the Genesis of Ketamine-Induced Perceptual Distortions and Hallucinatory States

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Brain and Mind

Abstract

The NMDA receptor (NMDAR) channel has been proposed to function as a coincidence-detection mechanism for afferent and reentrant signals, supporting conscious perception, learning, and memory formation. In this paper we discuss the genesis of distorted perceptual states induced by subanesthetic doses of ketamine, a well-known NMDA antagonist. NMDAR blockage has been suggested to perturb perceptual processing in sensory cortex, and also to decrease GABAergic inhibition in limbic areas (leading to an increase in dopamine excitability). We propose that perceptual distortions and hallucinations induced by ketamine blocking of NMDARs are generated by alternative signaling pathways, which include increase of excitability in frontal areas, and glutamate binding to AMPA in sensory cortex prompting Ca++ entry through voltage-dependent calcium channels (VDCCs). This mechanism supports the thesis that glutamate binding to AMPA and NMDARs at sensory cortex mediates most normal perception, while binding to AMPA and activating VDCCs mediates some types of altered perceptual states. We suggest that Ca++ metabolic activity in neurons at associative and sensory cortices is an important factor in the generation of both kinds of perceptual consciousness.

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  1. State University of São Paulo (UNESP), Institute of Biosciences, 18618-000, Botucatu, São Paulo, Brazil

    Alfredo Pereira Jr.

  2. Brain-Behavioral Sciences Research Consultant, 927 Manchester Ct, Charlottesville, Virginia, 22901, USA

    Gene Johnson

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  1. Alfredo Pereira Jr.
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Pereira, A., Johnson, G. Toward an Explanation of the Genesis of Ketamine-Induced Perceptual Distortions and Hallucinatory States. Brain and Mind 4, 307–326 (2003). https://doi.org/10.1023/B:BRAM.0000005466.28582.27

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