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Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice

Abstract:
Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41398-022-01846-9

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author
ORCID:
0000-0001-5371-7257
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author
ORCID:
0000-0003-0212-2880
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author
ORCID:
0000-0002-1885-3963
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Oxford college:
Merton College
Role:
Author
ORCID:
0000-0002-1426-2816
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author


Publisher:
Springer Nature
Journal:
Translational Psychiatry More from this journal
Volume:
12
Issue:
1
Article number:
77
Place of publication:
United States
Publication date:
2022-02-23
Acceptance date:
2022-02-03
DOI:
EISSN:
2158-3188
Pmid:
35197453


Language:
English
Keywords:
Subjects:
Pubs id:
1241200
Local pid:
pubs:1241200
Deposit date:
2023-04-15

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