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Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice

View ORCID ProfileJoanes Grandjean, David Buehlmann, Michaela Buerge, Hannes Sigrist, Erich Seifritz, Franz X. Vollenweider, Christopher R. Pryce, Markus Rudin
doi: https://doi.org/10.1101/751255
Joanes Grandjean
Singapore Bioimaging Consortium, Agency for Science, Technology and Research, University and ETH ZurichInstitute for Biomedical Engineering, University and ETH Zurich
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  • ORCID record for Joanes Grandjean
  • For correspondence: Joanes.Grandjean@radboudumc.nl
David Buehlmann
Institute for Biomedical Engineering, University and ETH Zurich
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Michaela Buerge
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich
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Hannes Sigrist
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich
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Erich Seifritz
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of ZurichCenter for Neuroscience Research, University and ETH Zurich
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Franz X. Vollenweider
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of ZurichCenter for Neuroscience Research, University and ETH Zurich
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Christopher R. Pryce
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of ZurichCenter for Neuroscience Research, University and ETH Zurich
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Markus Rudin
Institute for Biomedical Engineering, University and ETH ZurichInstitute of Pharmacology and Toxicology, University of Zurich
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Abstract

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that is involved in self-reference and displays altered FC in depressive disorders. In this study we investigated the effects of psilocybin on FC in the analogue of the DMN in mouse, with a view to establishing an experimental animal model to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin-relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interaction between 5-HT- and DA-regulated neural networks contributes to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.

Footnotes

  • https://openneuro.org/datasets/ds001725

  • https://openneuro.org/datasets/ds002154

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 01, 2019.
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Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
Joanes Grandjean, David Buehlmann, Michaela Buerge, Hannes Sigrist, Erich Seifritz, Franz X. Vollenweider, Christopher R. Pryce, Markus Rudin
bioRxiv 751255; doi: https://doi.org/10.1101/751255
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Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
Joanes Grandjean, David Buehlmann, Michaela Buerge, Hannes Sigrist, Erich Seifritz, Franz X. Vollenweider, Christopher R. Pryce, Markus Rudin
bioRxiv 751255; doi: https://doi.org/10.1101/751255

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