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bioRxiv · 10.1101/2023.09.26.559594

The most prominent electrophysiological effect of ketamine is not sufficient to cause anesthesia

Acland, B. T.·Palanca, B. J. A.·Bijsterbosch, J. D.·Snyder, L. H.
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Abstract

Electrophysiological recordings during ketamine anesthesia have revealed a slow alternating pattern of high- and low- frequency activity (a "gamma-burst" pattern) that develops with the onset of general anesthesia. We examine the role of NMDA receptor antagonism in generating the gamma-burst pattern and the link between gamma-bursts and dissociative anesthesia. We compare the effects of ketamine with those of the highly selective NMDA receptor antagonist CGS 19755 on multi-site intracranial electrophysiology and behavior in rhesus macaques. Remarkably, we find that animals given a moderate dose of CGS 19755 are able to perform a difficult memory task, while at the same time showing electrophysiological activity similar to ketamine anesthesia, with one key difference: a lack of delta-band LFP modulation. This difference demonstrates that ketamines ability to drive strong delta-band oscillations relies on additional mechanisms beyond NMDA receptor antagonism alone, and points to a key role for the activity underlying delta-band oscillations in causing anesthesia.

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Acland, B. T., Palanca, B. J. A., Bijsterbosch, J. D., Snyder, L. H.. 2023-09-27. The most prominent electrophysiological effect of ketamine is not sufficient to cause anesthesia. https://doi.org/10.1101/2023.09.26.559594

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