Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats
IntroductionPsilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modula...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1152578/full |
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| author | Filip Tylš Filip Tylš Čestmír Vejmola Čestmír Vejmola Vlastimil Koudelka Václava Piorecká Václava Piorecká Lukáš Kadeřábek Marcel Bochin Marcel Bochin Tomáš Novák Tomáš Novák Martin Kuchař Martin Kuchař Zdeňka Bendová Martin Brunovský Martin Brunovský Jiří Horáček Jiří Horáček Tomáš Pálení ček Tomáš Pálení ček |
| author_facet | Filip Tylš Filip Tylš Čestmír Vejmola Čestmír Vejmola Vlastimil Koudelka Václava Piorecká Václava Piorecká Lukáš Kadeřábek Marcel Bochin Marcel Bochin Tomáš Novák Tomáš Novák Martin Kuchař Martin Kuchař Zdeňka Bendová Martin Brunovský Martin Brunovský Jiří Horáček Jiří Horáček Tomáš Pálení ček Tomáš Pálení ček |
| author_sort | Filip Tylš |
| collection | DOAJ |
| description | IntroductionPsilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model.MethodsSelective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology.ResultsPsilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1–25 Hz; however, decreases in 25–40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect.DiscussionThese findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics. |
| first_indexed | 2024-03-13T03:54:06Z |
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| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-13T03:54:06Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-ad15f5638c4f48e7bb7ca5492d89072c2023-06-22T08:03:04ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-06-011710.3389/fnins.2023.11525781152578Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in ratsFilip Tylš0Filip Tylš1Čestmír Vejmola2Čestmír Vejmola3Vlastimil Koudelka4Václava Piorecká5Václava Piorecká6Lukáš Kadeřábek7Marcel Bochin8Marcel Bochin9Tomáš Novák10Tomáš Novák11Martin Kuchař12Martin Kuchař13Zdeňka Bendová14Martin Brunovský15Martin Brunovský16Jiří Horáček17Jiří Horáček18Tomáš Pálení ček19Tomáš Pálení ček20Psychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, CzechiaFaculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, CzechiaForensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaPsychedelic Research Centre, National Institute of Mental Health, Klecany, Czechia3rd Faculty of Medicine, Charles University in Prague, Prague, CzechiaIntroductionPsilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model.MethodsSelective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology.ResultsPsilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1–25 Hz; however, decreases in 25–40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect.DiscussionThese findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics.https://www.frontiersin.org/articles/10.3389/fnins.2023.1152578/fullserotonergic psychedelicspsilocybin/psilocinmodel of acute psychosisquantitative EEGpower spectraphase-lagged coherence |
| spellingShingle | Filip Tylš Filip Tylš Čestmír Vejmola Čestmír Vejmola Vlastimil Koudelka Václava Piorecká Václava Piorecká Lukáš Kadeřábek Marcel Bochin Marcel Bochin Tomáš Novák Tomáš Novák Martin Kuchař Martin Kuchař Zdeňka Bendová Martin Brunovský Martin Brunovský Jiří Horáček Jiří Horáček Tomáš Pálení ček Tomáš Pálení ček Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats Frontiers in Neuroscience serotonergic psychedelics psilocybin/psilocin model of acute psychosis quantitative EEG power spectra phase-lagged coherence |
| title | Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats |
| title_full | Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats |
| title_fullStr | Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats |
| title_full_unstemmed | Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats |
| title_short | Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats |
| title_sort | underlying pharmacological mechanisms of psilocin induced broadband desynchronization and disconnection of eeg in rats |
| topic | serotonergic psychedelics psilocybin/psilocin model of acute psychosis quantitative EEG power spectra phase-lagged coherence |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1152578/full |
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