Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.
D P Effinger, J L Hoffman, S G Quadir, C S Rollison, D Toedt, M Echeveste Sanchez, M W High, C W Hodge, M A Herman
Nature communications April 10, 2026 Peer reviewed DOI: 10.1038/s41467-026-71481-1 via PubMed
Summary
Psilocin, the active metabolite of psilocybin, influences brain activity differently in male and female rats. It increased expression of c-Fos in the paraventricular nucleus of the thalamus (PVT) and engaged PVT→CeA neurons in females but not males. Psilocin also heightened PVT's response to an aversive stimulus, particularly in passive responders. These results suggest that psilocin modulates emotional brain circuits in a sex-specific manner, providing insights into its potential therapeutic mechanisms.
Study at a glance
| Population | rats |
|---|---|
| Key finding | Psilocin administration increased PVT c-Fos expression and selectively engaged PVT→CeA neurons in females, enhancing reactivity to stimuli. |
Abstract
The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administration increased PVT c-Fos expression and selectively engaged PVT→CeA neurons in females, but not males. Psilocin enhanced PVT reactivity to an aversive air-puff stimulus, with effects primarily driven by passive responders. In PVT→CeA neurons, psilocin prevented time-dependent reductions in stimulus-evoked activity and maintained reactivity across timepoints in females but not males. The sustained engagement of PVT→CeA circuitry was driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry and behavior by psilocin, implicating PVT→CeA circuitry in the neural and behavioral effects of psychedelic compounds, advancing our understanding of how psychedelics modulate emotional brain circuits to further inform potential therapeutic mechanisms.