Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress
Translational Psychiatry June 14, 2025 Ines Erkizia-Santamaría, Igor Horrillo, Nerea Martínez-Álvarez et al. 16 citations
In a mouse model of chronic unpredictable mild stress, two doses of psilocybin (1 mg/kg, given 7 days apart) reversed stress-induced anhedonia and behavioral despair, but not apathy-related behavior. Psilocybin also produced an anxiolytic-like effect. However, it did not reverse stress-induced physiological signs of a hyperactive HPA axis or restore decreased brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Psilocybin increased expression and function of serotonin-2A receptors in the cortex of both control and stressed mice, and selectively increased glucocorticoid receptor expression in the cortex of stressed mice. These findings suggest psilocybin can rescue certain depressive and anxiety-like behaviors without normalizing all stress-related physiological or neuroplasticity impairments.