Serotonin Transporter and Plasma Membrane Monoamine Transporter Are Necessary for the Antidepressant-Like Effects of Ketamine in Mice
International Journal of Molecular Sciences October 1, 2020 M. Bowman, M. Vitela, K. Clarke et al.
Ketamine rapidly inhibits the clearance of serotonin from the hippocampus in mice, an effect that depends on the serotonin transporter (SERT) and the plasma membrane monoamine transporter (PMAT). In mice lacking either SERT or PMAT, ketamine no longer slows serotonin clearance and fails to produce antidepressant-like effects in the forced swim test. The findings suggest that ketamine's ability to block serotonin reuptake via both transporters may contribute to its rapid antidepressant action, alongside its known NMDA receptor antagonism. This work may guide development of depression treatments with fewer side effects than ketamine.