Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats
Evan Fuini, Arnold Chang, Josh Edwards, Marc Latta, Elias Gonzalez, Bryce Axe, Ashwath Maheswari, Richard J. Ortiz, Md Taufiq Nasseef, Taylor J. Woodward, Noah Cavallaro, Heather B. Bradshaw, Praveen P Kulkarni, Craig F. Ferris
Frontiers in Neuroscience May 1, 2025 DOI: 10.3389/fnins.2025.1554049 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Drug naive female and male rats |
| Intervention | Psilocybin |
| Dose | 0.03 mg/kg, 0.3 mg/kg, 3.0 mg/kg |
| Duration | 20 min BOLD recording; resting state connectivity collected approximately 35 min post injection |
| Topics | Psilocybin |
| Keywords | Hallucinogen Thalamus Basal ganglia Somatosensory system Prefrontal cortex Hippocampal formation |
| Citations | 6 |
| Data | OPAL OPAL |
| Key findings | Psilocybin caused a significant dose-dependent increase in positive BOLD signal in the somatosensory cortex, basal ganglia, and thalamus, with females showing greater activation than males at 0.3 mg/kg. |
Abstract
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. We hypothesized that psilocybin would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. These levels were validated by measuring psilocybin and its metabolite, psilocin. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection. All data were registered to rat 3D MRI atlas with 169 brain areas providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Males and females showed different sensitivity to psilocybin dose, with females exhibiting greater activation than males at 0.3 mg/kg, especially in thalamic and basal ganglia regions. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli, such as the cortico-striato-thalamo-cortical circuit and the claustrum, showed increased activation at higher doses of psilocybin. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.
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 6
- Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence Neuropsychopharmacology February 18, 2026
- Beyond the toad's kiss: Mapping acute 5-MeO-DMT effects on brain connectivity across sex and dose using awake rat neuroimaging Neuropharmacology March 6, 2026
- Psychedelics and the thalamocortical system: A scoping review Pharmacology, Biochemistry, and Behavior July 9, 2026
- Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats. Neuroscience Bulletin May 21, 2026
- Filtering the noise: a cerebellar-centered framework for understanding and treating mental illness -a paradigm shift in psychiatry Frontiers in Psychiatry April 13, 2026
and 1 more in the library
Cites 44
- 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
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 39 more in the library