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5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden; Research Group in Neuroscience and Experimental Psychology, Federal University of Vale do São Francisco, Petrolina, Brazil.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
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2023 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 6, no 1, article id 737Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 6, no 1, article id 737
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Neurosciences
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URN: urn:nbn:se:umu:diva-212740DOI: 10.1038/s42003-023-05093-6ISI: 001036816200001PubMedID: 37495733Scopus ID: 2-s2.0-85165914559OAI: oai:DiVA.org:umu-212740DiVA, id: diva2:1787561
Funder
Olle Engkvists stiftelseHedlund foundationPromobilia foundationStiftelsen Sigurd och Elsa Goljes minneWenner-Gren FoundationsAvailable from: 2023-08-14 Created: 2023-08-14 Last updated: 2023-08-14Bibliographically approved

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Brys, IvaniPetersson, Per

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