Comparative metabolomic analysis in plasma and cerebrospinal fluid of humans and in plasma and brain of mice following antidepressant-dose ketamine administration
Translational Psychiatry May 2, 2022 Ruin Moaddel, Panos Zanos, Cristan A Farmer et al. 32 citations
Subanesthetic-dose ketamine produces rapid antidepressant effects, but its mechanism remains unclear. A targeted metabolomic analysis of plasma and cerebrospinal fluid from nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg), along with parallel analysis in mice given ketamine, (2R,6R)-hydroxynorketamine (HNK), or saline, found that both ketamine and HNK affect multiple inflammatory pathways. Some changes were unique to humans or mice, suggesting species differences. Consistently implicated mechanisms across both species and sample types include LAT1, IDO1, NAD+, nitric oxide signaling, and the sphingolipid rheostat.