GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice.
The International Journal of Neuropsychopharmacology October 1, 2024 Nicholas E Bulthuis, Josephine C McGowan, Liliana R Ladner et al. 2 citations
Ketamine, a rapid-acting antidepressant, requires a specific NMDA receptor subunit (GluN2B) on adult-born neurons in the hippocampus to produce its effects, but this requirement differs between sexes. In male mice, GluN2B on 6-week-old adult-born neurons is necessary for ketamine to reduce behavioral despair, suppress feeding anxiety, and alter fear behavior. In female mice, GluN2B on these neurons is needed only for reducing feeding anxiety. Removing GluN2B from younger 2-week-old neurons did not replicate these effects. Eliminating adult neurogenesis increased fear expression, which ketamine administration counteracted. These findings indicate that 6-week-old adult-born hippocampal neurons partially mediate ketamine's rapid antidepressant actions, suggesting a target for improving treatment efficacy.