Characteristic patterns of EEG oscillations in sheep (Ovis aries) induced by ketamine may explain the psychotropic effects seen in humans

A U Nicol,A J Morton

doi:10.1038/s41598-020-66023-8

Abstract

Ketamine is a valuable anaesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (EEG) response to ketamine of 12 sheep. Following ketamine administration, EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0–125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterised by short periods (2–3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating EEG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical EEG activity. This persisted for up to several minutes, after which cortical activity resumed. This phenomenon is likely to explain the ‘k-hole’, a state of oblivion likened to a near death experience that is keenly sought by ketamine abusers.

Highlights

Ketamine is a neuroactive phencyclidine derivative highly valued for its anaesthetic and analgesic properties[1,2]
In addition to its well-described uses in the fields of anaesthesia, analgesia and drug abuse, ketamine has emerging applications in two other fields. It has not been implicated in long-term psychotic reactions in normal subjects, ketamine has been of interest in schizophrenia research for many years because it can precipitate the emergence of psychosis in schizophrenic patients[10]
Ketamine is highly valued for its anaesthetic and analgesic properties, yet few studies have examined in detail the EEG response to this drug

Summary

Introduction

Ketamine is a neuroactive phencyclidine derivative highly valued for its anaesthetic and analgesic properties[1,2]. In addition to its well-described uses in the fields of anaesthesia, analgesia and drug abuse, ketamine has emerging applications in two other fields It has not been implicated in long-term psychotic reactions in normal subjects, ketamine has been of interest in schizophrenia research for many years because it can precipitate the emergence of psychosis in schizophrenic patients[10]. Sheep have been recognised as a species that is eminently suitable for use as pre-clinical models of human neurological disorders[17,18] They have a large complex brain with a gyrencephalic cerebral cortex and basal ganglia that are anatomically similar to those of non-human primates. This phenomenon is likely to explain the ‘k-hole’ described and keenly sought by ketamine abusers[11]

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