Ketamine's rapid and sustained antidepressant effects are driven by distinct mechanisms.

ABSTRACT: Administration of multiple subanesthetic doses of ketamine increases the duration of antidepressant effects relative to a single ketamine dose, but the mechanisms mediating this sustained effect are unclear. Here, we demonstrate that ketamine's rapid and sustained effects on affective behavior are mediated by separate and temporally distinct mechanisms. The rapid effects of a single dose of ketamine result from increased activity of immature neurons in the hippocampal dentate gyrus without an increase in neurogenesis. Treatment with six doses of ketamine over two weeks doubled the duration of behavioral effects after the final ketamine injection. However, unlike ketamine's rapid effects, this more sustained behavioral effect did not correlate with increased immature neuron activity but ins

SUBMITTER: Rawat R 

PROVIDER: S-EPMC10899278 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature