Gestational psychedelic exposure disrupts brain development and offspring behavior in mice
Courtney, Y.; Anderson, J. M.; Lagares-Linares, C.; WENTHUR, C. J.; Lehtinen, M. K.
Show abstract
Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg kg-1) crossed the placenta, appearing in embryonic cerebrospinal fluid (CSF) within minutes at E12.5 and E16.5. Within 30 minutes, LSD and other serotonergic psychedelics induced a 5-HT2C agonist-like response in the choroid plexus, triggering apical remodeling and increasing CSF protein. A single E12.5 exposure altered cerebral cortical laminar organization and composition at postnatal day 8, and repeated dosing (E12.5-E16.5) amplified male-biased shifts from SATB2+ to CTIP2+ neuronal identities and increased microglia. Adult offspring showed reduced prepulse inhibition (male-predominant) and rotational stereotypy. These data identify an embryo-facing interface that detects maternal psychedelics and link CSF access to enduring neurodevelopmental and behavioral consequences.
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