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

AU Nicol, Jennifer Morton, Apollo-University Of Cambridge Repository
2020
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
more » ... e 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. Ketamine is a neuroactive phencyclidine derivative highly valued for its anaesthetic and analgesic properties 1,2 . Used in both medicine 3 and veterinary medicine 4 it has a rapid onset of action and does not cause respiratory depression 5 . Termed a 'dissociative' anaesthetic, it causes a characteristic anaesthesia whereby patients are catatonic and do not appear to process information, yet can swallow and open their eyes 3 . The analgesic effects of ketamine occur at lower concentrations than its anaesthetic effects, and persist beyond emergence from anaesthesia 6 . Ketamine is particularly valuable as an anaesthetic and analgesic where resources are limited, such as in field situations and developing countries. These qualities have earned ketamine its place on the World Health Organisation's essential drug list 7 . The dissociative state induced by ketamine almost certainly underlies its appeal as a recreational drug 8 . Psychic sensations associated with emergence from ketamine anaesthesia are frequently reported, and because of this, clinical use of ketamine is largely restricted to veterinary medicine and young or elderly human patients 9 . Subjective effects include perceptual distortions, sensations of floating, vivid dreams or illusions, distortion of sense of time and space, and alterations in mood state and body awareness 10 . At a sufficiently high dose, both awareness of self and surroundings, and interactions with others become profoundly impaired -a state known as the 'k-hole' 11 . Dissociation of the conscious from the physical self under the influence of ketamine is substantiated in psychophysiological studies in normal subjects (e.g. the false hand illusion 12 ). In addition to its well-described uses in the fields of anaesthesia, analgesia and drug abuse, ketamine has emerging applications in two other fields. Although 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 . It is being used to develop animal models of open Scientific RepoRtS | (2020) 10:9440 | https://doi.
doi:10.17863/cam.55520 fatcat:hfyvzcrywjh73mrowko5opmrl4