Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.
Synapse (New York, N.Y.) November 1, 2025 Oliver H Miller, Nils Grabole, Isabelle Wells et al.
A single low dose of ketamine rapidly lifts mood in people with treatment-resistant depression, with effects lasting up to a week. To understand how, researchers mapped the complete set of proteins being made in the mouse prefrontal cortex after a ketamine dose. They found that ketamine broadly turns on protein synthesis, especially in pathways related to cell signaling, metabolism, blood vessel growth, and structural brain changes. One gene, VIPR2, which makes a receptor for a brain peptide, stood out. This receptor appears only on a specific type of inhibitory neuron. Activating that receptor with a drug changed how nearby brain cells fired and disrupted their coordinated activity, yet it still produced an antidepressant effect in mice, suggesting a new target for depression treatments.