Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms
Justyna K. Hinchcliffe, Christopher W. Thomas, Gary Gilmour, Emma Robinson
bioRxiv (Cold Spring Harbor Laboratory) January 15, 2026 preprint DOI: 10.64898/2026.01.14.699553 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| Population | Rats with chronic interferon-alpha-induced depression |
| Intervention | Psilocybin |
| Dose | 0.3 mg/kg |
| Duration | 24 hours to at least 7 days |
| Topics | Psilocybin Serotonin |
| Keywords | Antidepressant Anhedonia Rat model Depression economics Imipramine Pharmacology Hallucinogen Depressive symptoms |
| Key points | Acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24 hours, with effects enduring for at least 7 days in a rat model of depression. |
Abstract
Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha–induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This suggests psilocybin can restore blunted reward processing, an effect which could significantly contribute to its sustained antidepressant 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
Cites 6
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Psilocybin desynchronizes the human brain. Nature August 1, 2024
- Rapid-acting antidepressant drugs modulate affective bias in rats Science Translational Medicine January 10, 2024
and 1 more in the library