Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2.
Neuron May 1, 2022 J. Lopez, M. Lücken, E. Brivio et al. 78 citations
A single low dose of ketamine produces a rapid and lasting antidepressant effect in mice, but the molecular mechanisms are unclear. This work identifies Kcnq2 gene activity in glutamatergic neurons of the ventral hippocampus as a key regulator of ketamine's sustained action. Combining ketamine with retigabine, a KCNQ activator, enhanced antidepressant-like effects, an effect not seen with the classical antidepressant escitalopram. These findings advance understanding of ketamine's sustained antidepressant mechanisms and suggest potential clinical applications.