Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
OpenAlex – September 01, 2019
Source: OpenAlex
Summary
Psilocybin, a potent hallucinogen, profoundly reconfigures brain activity, offering new insights into its therapeutic potential. Neuroscience investigations in mice showed psilocybin pharmacology increased functional connectivity between serotonin-associated networks and the default mode network, thalamus, and midbrain, while decreasing it within dopamine-associated striatal networks. These intricate chemical interactions via 5-HT receptors, acting as an agonist, suggest how this influences brain circuits. Understanding this neurotransmitter receptor influence on behavior is crucial for developing new psychedelics and drug studies for brain disorders and psychology.
Abstract
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.