RT Journal Article
SR Electronic
T1 Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 751255
DO 10.1101/751255
A1 Joanes Grandjean
A1 David Buehlmann
A1 Michaela Buerge
A1 Hannes Sigrist
A1 Erich Seifritz
A1 Franz X. Vollenweider
A1 Christopher R. Pryce
A1 Markus Rudin
YR 2019
UL http://biorxiv.org/content/early/2019/09/01/751255.abstract
AB 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.