“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

Vigilance states - waking, slow-wave sleep (SWS) and paradoxical sleep, are thought to be controlled by several cortical and subcortical neuromodulatory circuits, among which the serotonergic (5-HT) system plays an important role. Recently, serotonergic psychedelics have attracted attention as potent antidepressants. While they are known to induce profound changes in subjective experience, the immediate and delayed effects of psychedelics on classical signatures of sleep-wake states remain under-investigated. To address this, we performed chronic electrophysiological recordings in the cortex of freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5- MeO-DMT). The most noticeable effect of 5-MeO-DMT administration was the suppression of paradoxical sleep and an acute induction of a mixed state of vigilance, characterised instead by prominent SWS-like slow waves on the EEG and LFP in awake, moving animals. We posit that the occurrence of this state in mice, which we refer to as “paradoxical wakefulness”, may be a rodent equivalent of the altered state of consciousness induced by psychedelics in humans.