ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice.

ABSTRACT: Rapastinel as the allosteric modulator of N-methyl-D-aspartate receptor (NMDAR) produces rapid antidepressant-like effects dependent on brain-derived neurotrophic factor (BDNF) and VGF (nonacryonimic) release. Herein, we further explore the molecular mechanisms of the antidepressant effects of repeated administration with rapastinel in mice. Our results showed that continuous 3-day rapastinel (5 and 10 mg/kg, i.v.) produced antidepressant-like actions dependent on the increase in extracellular regulated protein kinase (ERK)/mammalian target of rapamycin (mTOR) signaling and downstream substrates p70S6 kinase (p70S6k) and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which may induce the expression of VGF and BDNF in the hippocampus and prefrontal cortex of mice. Furthermo

SUBMITTER: Shen M 

PROVIDER: S-EPMC9780240 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature