Sex-Specific Neuropsychiatric Effects of Subanesthetic Ketamine Exposure in Pregnant Mice and Their Offspring.
Cellular and molecular neurobiology July 19, 2025 Wei-Sheng Lin, Pei-Yu Wang, Sheng-Rong Yeh et al.
Pregnant mice given low-dose ketamine late in pregnancy showed less depression-like behavior. Their male adult offspring also displayed reduced depression- and anxiety-like behaviors, with no changes in social or memory performance. These behavioral effects in males were linked to increased dendritic spine density in the dentate gyrus of the hippocampus, while hippocampal neurogenesis and overall dendritic structure remained unchanged. Male embryos had higher expression of NMDA receptor subunits GluN2A and GluN3A in the hippocampus than females, indicating sex-dependent effects of ketamine on the developing brain. Prenatal ketamine exposure thus produces long-lasting, sex-specific neurobehavioral outcomes, with male offspring showing greater stress resilience.