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 DOI: 10.64898/2026.01.14.699553 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractPsilocybin, a serotonergic psychedelic, can rapidly and lastingly reverse impaired reward processing in a rat model of depression. In rats with chronic interferon-alpha-induced depression, a single dose of psilocybin (0.3 mg/kg) restored reward-induced behavioral biases within 24 hours, and the effect persisted for at least 7 days. This suggests that restoring blunted reward processing may contribute to psilocybin's sustained antidepressant effects.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| 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 |
| Key finding | 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.