Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.
Devin P. Effinger, J L Hoffman, Sema G. Quadir, Christian S Rollison, Daniel Toedt, Maria Echeveste Sanchez, Margaret W High, Clyde W. Hodge, Melissa A. Herman
Nature Communications April 10, 2026 DOI: 10.1038/s41467-026-71481-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Psilocin |
| Topics | Psilocybin |
| Citations | 1 |
| Key findings | Psilocin modulates PVT and PVT→CeA circuitry in a sex-specific manner, engaging these circuits in females but not males. |
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.