Xiaoxue Li

(2R,6R)-Hydroxynorketamine elicits rapid antidepressant effects by promoting astrocytic µ-δ opioid receptor heterodimerization

bioRxiv June 3, 2026 Yanxia 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...