The astrocytes in the prefrontal cortex contribute to the rapid antidepressant-like effects of psilocybin in the chronic restraint stress mouse model
Progress in Neuro-Psychopharmacology and Biological Psychiatry April 1, 2026 Yong-xing Qiao, Wei Dai, Yi-shan Yao et al. 1 citation
Psilocybin rapidly reversed depressive-like behaviors in mice subjected to chronic restraint stress, an effect comparable to ketamine. Both drugs prevented stress-induced loss of astrocytes and reduced levels of the A1 astrocyte marker C3 protein in the prefrontal cortex. The active metabolite psilocin stimulated primary astrocyte activation, proliferation, and release of ATP, lactate, and glutamate, and improved mitochondrial function. Psilocin also reversed impairments caused by A1 astrocytes. Depleting astrocytes in the prelimbic region of the medial prefrontal cortex diminished psilocybin's antidepressant action in unstressed mice, suggesting astrocytes play a key role in the drug's effects.