Nature communicationsApr 10, 2026

Psilocin increases activity in the brain's arousal center and its connection to the emotion center more in one sex

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 11, 2026

Abstract

Psilocin administration increased PVT c-Fos expression and selectively engaged PVT→CeA neurons in female rats.

Psilocin enhanced the reactivity of the paraventricular nucleus of the thalamus (PVT) to an aversive air-puff stimulus.
The effects of psilocin on PVT reactivity were primarily observed in passive responders.
In females, psilocin prevented time-dependent reductions in activity in PVT→CeA neurons, maintaining reactivity over time.
No similar effects were observed in male rats regarding the engagement of PVT→CeA neuronal activity.

Simplified

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.

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Competing interests

Competing interests: The authors declare no competing interests.

PubMed

Psilocin increases activity in the brain's arousal center and its connection to the emotion center more in one sex

Abstract

Full Text

Funding

Competing interests

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