Antidepressant-like effects of ketamine in a mouse model of serotonergic dysfunction.
Neuropharmacology February 12, 2020 C. Wilson, Shanshan Li, A. Hannan et al.
Mice lacking the serotonin transporter (5-HTT KO mice) model SSRI-resistant depression, showing no response to the SSRI sertraline in the forced-swim test, unlike wild-type mice. Ketamine, an NMDAR antagonist, produced antidepressant-like effects in both genotypes, suggesting it works independently of 5-HTT function. The KO mice also had reduced locomotor responses to NMDAR antagonists and lower hippocampal GluN2A protein, indicating glutamatergic dysfunction. These results support ketamine's effectiveness in treatment-resistant depression and offer a model to study its mechanisms.