Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2024 Ji-Woon Kim, Benjamin Kleinfelter, Ege T Kavalali et al. 3 citations
Ketamine, a rapidly acting antidepressant, works by restoring glutamate signaling in the hippocampus, countering the effects of a drug that induces depressed mood. Physostigmine, which triggers depression-like symptoms in humans, was found to cause long-term reduction of glutamate release in the mouse hippocampus. Ketamine rapidly re-establishes synaptic efficacy through postsynaptic signaling and masks the behavioral effects of physostigmine. The findings reveal that the synaptic mechanisms underlying mood changes differ from those behind antidepressant action, suggesting distinct pathways for neuropsychiatric disorders and their treatment.