Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F23%3A43927435" target="_blank" >RIV/60461373:22330/23:43927435 - isvavai.cz</a>

Result on the web

<a href="https://www-frontiersin-org.ezproxy.vscht.cz/articles/10.3389/fnins.2023.1152578/full" target="_blank" >https://www-frontiersin-org.ezproxy.vscht.cz/articles/10.3389/fnins.2023.1152578/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fnins.2023.1152578" target="_blank" >10.3389/fnins.2023.1152578</a>

Result language

angličtina

Original language name

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats

Original language description

Introduction: Psilocybin 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. Methods: Selective 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. Results: Psilocin-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. Discussion: These 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. Copyright © 2023

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/NU21-04-00307" target="_blank" >NU21-04-00307: Psilocybin versus ketamine – fast acting antidepressant strategies in treatment-resistant depression</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Neuroscience

ISSN

1662-4548

e-ISSN

1662-453X

Volume of the periodical

17

Issue of the periodical within the volume

2023-07-20

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

"nestrankovano"

UT code for WoS article

001019986200001

EID of the result in the Scopus database

2-s2.0-85164519166