Ketamine's rapid antidepressant effects are mediated by Ca²⁺-permeable AMPA receptors.

ABSTRACT: Ketamine is shown to enhance excitatory synaptic drive in multiple brain areas, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamine's therapeutic actions are likely mediated by enhancing neuronal Ca²⁺ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that reduces excitatory synaptic transmission and postsynaptic Ca²⁺ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca²⁺ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment in cultured mouse hippocampal neurons significantly reduces Ca²⁺ and calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphoryl

SUBMITTER: Zaytseva A 

PROVIDER: S-EPMC10319435 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature