Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin

Ross J. Purple; Rahul Gupta; Christopher W. Thomas; Caroline T. Golden; Nicola Palomero-Gallagher; Robin Carhartt-Harris; Sean Froudist-Walsh; Matthew W. Jones

doi:10.1038/s41380-025-03182-y

Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin

Ross J. Purple, Rahul Gupta, Christopher W. Thomas, Caroline T. Golden, Nicola Palomero-Gallagher, Robin Carhartt-Harris, Sean Froudist-Walsh, Matthew W. Jones

Molecular Psychiatry August 26, 2025 DOI: 10.1038/s41380-025-03182-y (opens in new tab)

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AI-extracted from the abstract

Characteristics	Observational cohort Peer reviewed
Population	Adult rats
Intervention	Psilocybin
Dose	0.3 mg/kg or 1 mg/kg i.p.
Duration	6 days post-injection
Topics	Psilocybin
Keywords	Hallucinogen Prefrontal cortex Term time Cognitive psychology Cognition
Citations	2
Key findings	Psilocybin induces 100 Hz oscillations in the infralimbic cortex and reduces neuronal firing rates acutely, followed by days-long increases in beta and low-gamma power in the same region.

Abstract

Abstract We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3 mg/kg or 1 mg/kg i.p.) unmasked 100 Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1 h post-injection and were accompanied by decreased net neuronal firing rates and reduced spike-train complexity. These acute effects were more prominent during resting behaviour than during performance of a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20–60 Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.

Comparable studies

Other preclinical and animal studies on psilocybin, most cited first.

Study	Year	Design
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

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