bioRxivJune 3, 2026Shuo Yang, Ling-Jun Wang, Yunxiang Sun et al.
preprint
Abstract A deeper understanding of the targets and mechanisms of fast-acting antidepressants, exemplified by ketamine, remains indispensable for better therapeutic strategies and understanding depression. Beyond the canonical neuron-centric NMDAR inhibition hypothesis, brain opioid system and glia-mediated processes are increasingly implicated in ketamine’s antidepressant efficacy, yet their...
Accumulating evidence suggests that glutamate clearance plays a critical role in the pathophysiology and treatment of depression. Preclinical and clinical studies have demonstrated that ketamine provides an immediate and sustained antidepressant effect. However, the precise mechanism of its action remains to be elucidated. Glutamate transporter 1 (GLT1) participates in glutamate clearance;...
Previous studies have suggested that rapid reductions in depression-like behaviors are observed in response to sub-anesthetic-doses of ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist. Neuropeptide VGF (non-acronymic) is a critical effector of depression-like behaviors and is thought to be involved in the antidepressant actions of ketamine that have been demonstrated. However, the...