Acute psilocin increased cortical activity in rat
Junhong Liu, Y. Lynn Wang, Ke Xia, Jia-Bin Wu, Danhao Zheng, Aoling Cai, Haitao Yan, Ruibin Su
Frontiers in Neuroscience February 4, 2026 DOI: 10.3389/fnins.2026.1593703 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Psilocin hydrochloride |
| Dose | 2.0 mg/kg |
| Duration | 10 minutes after injection |
| Measures | BOLD fMRI, immunofluorescence of EGR1 |
| Topics | Psilocybin |
| Keywords | Retrosplenial cortex Cortex anatomy Posterior cingulate Cerebral cortex Hippocampal formation Anterior cingulate cortex Premovement neuronal activity Hippocampus Infralimbic cortex Hallucinogen |
| Key findings | Psilocin increases brain activity and functional connectivity in rats, particularly in cortical and striatal regions, along with upregulation of EGR1. |
Abstract
Psilocin, a naturally occurring hallucinogenic component of magic mushrooms, exerts notable psychoactive effects in both humans and rodents. However, the underlying mechanisms remain not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a valuable tool in many preclinical and clinical trials for investigating changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocin on rats have not been thoroughly explored. This study aimed to explore the impact of psilocin on rats' brain activity by combining BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocin hydrochloride injection (2.0 mg/kg, i.p.), elevated brain activity was detected in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. Moreover, a region-of-interest (ROI) -wise FC analysis matrix indicated enhanced interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex with the cortical and striatal areas. In addition to the fMRI observations, acute psilocin led to an increase in the EGR1 level in most cortical and striatal regions, indicating a consistent activation throughout the cortical and striatal areas. In conclusion, the psilocin-induced hyperactive state in rats is congruent to that in humans, and the increased brain activity, enhanced functional connectivity and up-regulation of EGR1 may be responsible for its pharmacological effects.
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 2
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review International Journal of Molecular Sciences September 10, 2026
- Beyond head-twitch response: Acute psilocybin affects spontaneous behaviors in rats in a dose-dependent manner. Journal of Psychopharmacology August 25, 2026
Cites 30
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
and 25 more in the library