Abstract
Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the effects of tryptamine and phenethylamine psychedelics (psilocin 4 mg/kg, LSD 0.2 mg/kg, mescaline 100 mg/kg, and DOB 5 mg/kg) on EEG in freely moving rats. A system consisting of 14 cortical EEG electrodes, co-registration of behavioral activity of animals with subsequent analysis only in segments corresponding to behavioral inactivity (resting-state-like EEG) was used in order to reach a high level of translational validity. Analyses of the mean power, topographic brain-mapping, and functional connectivity revealed that all of the psychedelics irrespective of the structural family induced overall and time-dependent global decrease/desynchronization of EEG activity and disconnection within 1–40 Hz. Major changes in activity were localized on the large areas of the frontal and sensorimotor cortex showing some subtle spatial patterns characterizing each substance. A rebound of occipital theta (4–8 Hz) activity was detected at later stages after treatment with mescaline and LSD. Connectivity analyses showed an overall decrease in global connectivity for both the components of cross-spectral and phase-lagged coherence. Since our results show almost identical effects to those known from human EEG/MEG studies, we conclude that our method has robust translational validity.
Highlights
Serotonergic psychedelics are drugs that dramatically affect human perception, cognition and emotions, and induce socalled “altered state of consciousness” [1]. According to their binding core structure, psychedelics may be divided into two main chemical classes—tryptamine derivatives (e.g., lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), 5methoxy-dimethyltryptamine (5-MeO-DMT)) [2, 3], and phenethylamine derivatives (e.g., mescaline, 2,5-dimethoxy-4-bromoamphetamine (DOB)) [4]
In order to describe the phenomenology of the experience in animal studies scientists have to deal with behavioral experiments, such as evaluation of locomotion, exploratory behavior, sensorimotor processing, stereotyped behaviors, cognitive tasks, etc., which have all shown to be altered after psychedelics, but often have a limited translational validity to humans [13,14,15,16,17,18,19]
Until now we still do not know whether psychedelics induce visual perceptual changes in animals such as illusions and hallucinations, effects that are fundamental in humans [20]
Summary
Serotonergic psychedelics are drugs that dramatically affect human perception, cognition and emotions, and induce socalled “altered state of consciousness” [1]. According to their binding core structure, psychedelics may be divided into two main chemical classes—tryptamine derivatives (e.g., lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), 5methoxy-dimethyltryptamine (5-MeO-DMT)) [2, 3], and phenethylamine derivatives (e.g., mescaline, 2,5-dimethoxy-4-bromoamphetamine (DOB)) [4]. [10,11,12]) which may be evaluated by functional neuroimaging methods such as PET, fMRI, or EEG. Evaluating the electrical activity of the brain, in contrast to behavioral models, examines the biological processes of the same origin and very likely the same function. EEG, unlike other methods, can be used as a whole-brain neuroimaging tool in awake and freely moving animals
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