Vigilance state dissociation induced by 5-MeO-DMT in mice

TL;DR

This study shows that 5-MeO-DMT induces a brain state in mice that combines waking behavior with features of sleep, which may explain psychedelic effects like hallucinations.

Contribution

The study identifies a dissociated brain state induced by 5-MeO-DMT, combining waking behavior with sleep-like cortical activity.

Findings

5-MeO-DMT induces a dissociated state with slow cortical oscillations and pupil dilation in awake mice.

REM sleep is initially suppressed but overcompensated within 48 hours after 5-MeO-DMT administration.

Sleep deprivation followed by 5-MeO-DMT reduces the rebound of sleep slow-wave activity.

Abstract

Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of vigilance. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). We report an acute induction of a dissociated state, characterised by prominent slow oscillations in the cortex and marked pupil dilation in behaviourally awake, moving animals. REM sleep was initially markedly suppressed, but was overcompensated in the subsequent 48 hours, while administration of 5-MeO-DMT immediately after sleep deprivation attenuated the subsequent rebound of sleep slow-wave activity. We argue that the occurrence of a dissociated state combining features of waking and sleep may fundamentally underpin the known and hypothesised effects of psychedelics — from dream-like hallucinations to reopening of the critical period for plasticity.

Administration of 5-MeO-DMT produces a dissociated brain state in mice, characterized by global slow-wave activity alongside behavioral wakefulness and marked pupil dilation.

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