Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms

Hinchcliffe, J.; Thomas, C.; Gilmour, G.; Robinson, E.

doi:10.64898/2026.01.14.699553

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bioRxiv · 10.64898/2026.01.14.699553

Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms

Hinchcliffe, J.·Thomas, C.·Gilmour, G.·Robinson, E.

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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.

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Hinchcliffe, J., Thomas, C., Gilmour, G., Robinson, E.. 2026-01-15. Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms. https://doi.org/10.64898/2026.01.14.699553

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