Psilocybin selectively suppresses novelty-induced grooming via 5-HT2B receptors: A microstructure analysis in Wistar rats.
Alexandre Seillier, Ghinwa Ibrahim El Dannan, Lenka Seillier
Progress in Neuro-Psychopharmacology and Biological Psychiatry September 9, 2026 DOI: 10.1016/j.pnpbp.2026.111924 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | Psilocybin RS-127445 |
| Measures | Grooming Analysis Algorithm (GAA) |
| Topics | Psilocybin Serotonin |
| Keywords | Behavioral microstructure Grooming Rs-127445 Rat |
| Key findings | Psilocybin reduced novelty-induced grooming in Wistar rats, mainly by selectively suppressing abnormal, non-comfort grooming microstructure. RS-127445 reversed the psilocybin-induced reduction in total grooming time and bouts and blocked psilocybin's suppression of fragmented bout and aberrant transition patterns. The authors argue this demonstrates a role for 5-HT2B receptors in regulating complex, novelty-induced grooming activity. |
Abstract
Psilocybin, a tryptamine alkaloid found naturally in numerous Psilocybe mushroom species, is currently being investigated for its therapeutic potential in treating several neurobehavioral and psychiatric diseases. Our previous data showed that the 5-HT2B receptor (5-HT2BR) immobility and increases in climbing behavior in the forced swim test (FST), revealing that psilocybin's predictive validity in the FST can be dissociated from its 5-HT2A-mediated psychedelic effects. Assessing how psilocybin modulates other innate, ethologically relevant behaviors beyond the FST is critical to fully mapping its 5-HT2BR-dependent profile. Given the emerging relevance of self-grooming in modeling various affective brain disorders, studying its microstructure offers important insights into the complex neural regulation of behavioral sequences. Specifically, this study aimed to characterize the effect of psilocybin on novelty-induced grooming in Wistar rats using the Grooming Analysis Algorithm (GAA) and evaluated whether RS-127445 reversed these behavioral changes. Our data showed that psilocybin reduced grooming as quantified by traditional grooming measures (total grooming time and number of bouts), and that this reduction resulted from a selective suppression of abnormal, non-comfort behavioral grooming microstructure. RS-127445 reversed the psilocybin-induced reduction in traditional measures and blocked psilocybin's selective suppression of fragmented bout and aberrant transition patterns. These results extend our understanding of psilocybin's behavioral profile, demonstrating a novel role for the 5-HT2BRs in the regulation of complex, novelty-induced grooming activity.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: Psilocybin Supports
Psilocybin reduced novelty-induced grooming in rats mainly by selectively suppressing abnormal, non-comfort grooming microstructure, and this effect was reversed by a 5-HT2B receptor antagonist.
Synthesized
Comparable studies
Other preclinical and animal studies on serotonin, 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 | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 23
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
and 18 more in the library