Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.
Devin P. Effinger, Jessica L Hoffman, Sarah E Mott, Sarah N. Magee, Sema G. Quadir, Christian S Rollison, Daniel Toedt, Maria Echeveste Sanchez, Margaret W High, Clyde W. Hodge, Melissa A. Herman
Nature Communications June 22, 2024 DOI: 10.1038/s41467-024-49741-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Sprague Dawley rats |
| Intervention | Psilocin |
| Topics | Psilocybin |
| Keywords | Psychedelics Anxiety disorders Stress response Psilocybin research |
| Citations | 15 |
| Key findings | Psilocin increases PVN reactivity to an aversive stimulus in male rats, driven by active threat responders, but not in females. |
Abstract
Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 8
- Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice. Psychopharmacology May 17, 2025
- Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats. Neuropsychopharmacology April 19, 2025
- The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice. Molecular Psychiatry May 1, 2026
- Separate or inseparable? Serotonin and dopamine system interactions may underlie the therapeutic potential of psilocybin for anorexia nervosa Physiology & Behavior May 20, 2025
- Psilocybin induces sex- and context-specific recruitment of the stress axis Current Biology December 9, 2025
and 3 more in the library
Cites 23
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 18 more in the library