Adolescent exposure to the psychedelic 25C-NBOMe in rats induces lasting competitive avoidance through disrupted...

Psychedelics, known for prosocial effects and therapeutic potential in psychiatry, are often first used during adolescence, yet their enduring impact on social behavior and its underlying circuits remain unclear. Here we show that repeated exposure to the serotonergic psychedelic drug 25C-NBOMe during adolescence, but not exposure in adulthood, induced lasting competitive avoidance in male Sprague-Dawley rats-the most prominent change among several interrelated social behaviors and one that was not a collateral effect of altered sociability or social dominance. Multisite recordings revealed disrupted default mode network (DMN) synchrony, with reduced theta band coherence between the ventral hippocampus (vHPC) and the orbitofrontal cortex (OFC) most strongly predicting this behavioral change. Chemogenetic activation of the vHPC → OFC projection normalized the avoidance behavior in drug-exposed rats, whereas chemogenetic inhibition induced it in controls. These findings indicate that the vulnerability of DMN synchrony to psychedelics during adolescence can durably reshape adult social functioning.