# Subcortical targets involved in the action of psilocybin in learned and innate escape behaviors

> **NIH NIH F30** · YALE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT TITLE
Subcortical targets involved in the action of psilocybin in learned and innate escape behaviors
PROJECT SUMMARY
 Mood disorders such as depression now represent a leading cause of disability throughout the world,
with conventional first-line treatments failing to provide relief for most patients. In recent years, novel
treatments with fast-acting properties have garnered significant interest as innovative therapies. The
psychedelic psilocybin, in particular has recently gained attention for its ability to produce substantial and rapid
antidepressant effects in early-phase clinical trials. This combination of increasing need and exciting
preliminary clinical results has led to the recent ‘breakthrough therapy’ status designation for psilocybin to be
studied as a treatment for major depressive disorder. Yet despite these exciting results in pilot clinical trials, the
neurobiology underlying the effect of psilocybin remains less understood. Thus, a critical opportunity to further
our understanding of the action of psilocybin will be addressed here.
 Among early studies examining the mechanisms of action of psilocybin, most have focused on the
neocortex and hippocampus. However, previous cellular and circuit-level research has clearly implicated
subcortical structures as key in the action of psilocybin. Our own preliminary work using whole-brain cFos
mapping has identified several candidate subcortical regions that are modulated by psilocybin. Aim 1 will
determine the activity of two of these key subcortical brain regions via in vivo recording with high-density silicon
probes to determine how neural activity changes following systemic psilocybin administration. Aim 2 will use
causal manipulation during psilocybin treatment to determine the relative role of subcortical regions during
innate and learned escape behaviors in mice. Specifically, chemogenetics will be used to bidirectionally control
brain region activity during a looming stimulus and learned escape behavioral paradigms. Cumulatively, this
work will determine the relative roles of key subcortical brain regions in the action of psilocybin during escape
behaviors and expand the framework for psilocybin’s use in clinical treatment.

## Key facts

- **NIH application ID:** 10828325
- **Project number:** 5F30DA059437-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Pasha A Davoudian
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-04-16 → 2026-04-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828325

## Citation

> US National Institutes of Health, RePORTER application 10828325, Subcortical targets involved in the action of psilocybin in learned and innate escape behaviors (5F30DA059437-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10828325. Licensed CC0.

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