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...
bioRxivJune 3, 2026Yanxia Liang, Lingjun Wang, Yajie Li et al.
preprint
Ketamine produces rapid antidepressant effects but is constrained by psychotomimetic properties and abuse potential. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) shows antidepressant-like efficacy without N-methyl-D-aspartate receptor (NMDAR) blockade, yet its upstream targets remain unclear. Here we show that HNK potentiates hippocampal excitatory transmission and reverses...
The mechanisms underlying the rapid-acting antidepressant effects of ketamine have not been fully identified. In current study, we observed that a single subanesthesia dose of ketamine strongly decreased the immobility time of Sprague–Dawley rats in forced swim test. Ketamine injection significantly increased GluR1 expression and GluR1 Ser845 phosphorylation in prefrontal cortex....