Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons.

ABSTRACT: Dysregulation of the glutamatergic system and its receptors in medial prefrontal cortex (mPFC) has been implicated in major depressive disorder. Recent preclinical studies have shown that enhancing NMDA receptor (NMDAR) activity can exert rapid antidepressant-like effects. AGN-241751, an NMDAR positive allosteric modulator (PAM), is currently being tested as an antidepressant in clinical trials, but the mechanism and NMDAR subunit(s) mediating its antidepressant-like effects are unknown. We therefore used molecular, biochemical, and electrophysiological approaches to examine the cell-type-specific role of GluN2B-containing NMDAR in mediating antidepressant-like behavioral effects of AGN-241751. We demonstrate that AGN-241751 exerts antidepressant-like effects and reverses behavioral defici

SUBMITTER: Pothula S 

PROVIDER: S-EPMC8027594 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature