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
Affiliations
Joanes Grandjean
Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore; Institute for Biomedical Engineering, University and ETH Zurich, Switzerland; Correspondence to: PO Box 9101, 6500HB Nijmegen, the Netherlands.
David Buehlmann
Institute for Biomedical Engineering, University and ETH Zurich, Switzerland
Michaela Buerge
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
Hannes Sigrist
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
Erich Seifritz
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Center for Neuroscience Research, University and ETH Zurich, Switzerland
Franz X. Vollenweider
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Center for Neuroscience Research, University and ETH Zurich, Switzerland
Christopher R. Pryce
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland; Center for Neuroscience Research, University and ETH Zurich, Switzerland
Markus Rudin
Institute for Biomedical Engineering, University and ETH Zurich, Switzerland; Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
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 displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view 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 cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute 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.
