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5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system

Brys, Ivani LU ; Barrientos, Sebastian A LU orcid ; Ward, Jon Ezra ; Wallander, Jonathan ; Petersson, Per LU and Halje, Pär LU (2023) In Communications Biology 6(1).
Abstract

The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably,... (More)

The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably, the phase differences between structures were close to zero, corresponding to <1 ms delays. Likely, this hypersynchrony has major effects on the integration of information across neuronal systems and we propose that it is a key contributor to changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Biology
volume
6
issue
1
article number
737
publisher
Nature Publishing Group
external identifiers
  • scopus:85165914559
  • pmid:37495733
ISSN
2399-3642
DOI
10.1038/s42003-023-05093-6
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
52e7ada8-13e9-4931-b48b-69f58ebeeacd
date added to LUP
2023-08-01 11:01:16
date last changed
2024-04-20 02:38:34
@article{52e7ada8-13e9-4931-b48b-69f58ebeeacd,
  abstract     = {{<p>The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably, the phase differences between structures were close to zero, corresponding to &lt;1 ms delays. Likely, this hypersynchrony has major effects on the integration of information across neuronal systems and we propose that it is a key contributor to changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.</p>}},
  author       = {{Brys, Ivani and Barrientos, Sebastian A and Ward, Jon Ezra and Wallander, Jonathan and Petersson, Per and Halje, Pär}},
  issn         = {{2399-3642}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system}},
  url          = {{http://dx.doi.org/10.1038/s42003-023-05093-6}},
  doi          = {{10.1038/s42003-023-05093-6}},
  volume       = {{6}},
  year         = {{2023}},
}