5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats

TY - JOUR

T1 - 5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats

AU - Souza, Annie C

AU - Souza, Bryan C

AU - França, Arthur

AU - Moradi, Marzieh

AU - Souza, Nicholy C

AU - Leão, Katarina E

AU - Tort, Adriano B L

AU - Leão, Richardson N

AU - Lopes-Dos-Santos, Vítor

AU - Ribeiro, Sidarta

N1 - © 2024. The Author(s).

PY - 2024/5

Y1 - 2024/5

N2 - 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

AB - 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

KW - Animals

KW - Prefrontal Cortex/drug effects

KW - Rats

KW - Hippocampus/drug effects

KW - Wakefulness/drug effects

KW - Male

KW - Sleep/drug effects

KW - Electroencephalography

KW - Theta Rhythm/drug effects

KW - Hallucinogens/pharmacology

U2 - 10.1038/s41598-024-61474-9

DO - 10.1038/s41598-024-61474-9

M3 - Article

C2 - 38760450

SN - 2045-2322

VL - 14

SP - 11281

JO - Scientific Reports

JF - Scientific Reports

IS - 1

ER -