Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress.
Neuropsychopharmacol Rep September 1, 2026 Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.
In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.