High-frequency oscillations in the mammalian brain after ketamine and other NMDA receptor antagonists.
Journal of psychopharmacology (Oxford, England) July 24, 2025 Mark Jeremy Hunt, Jacek Wróbel
Subanesthetic doses of ketamine produce rapid psychotomimetic and long-lasting antidepressant effects, yet its mechanisms remain unclear. Neurophysiological recordings in freely moving rodents reveal that ketamine and other NMDAR antagonists markedly enhance high-frequency oscillations (HFO, >100 Hz) across olfactory and frontostriatal brain regions. This rhythm is remarkably coherent across distinct regions, modulated by slower oscillations, and driven largely by respiration-locked olfactory bulb activity. Similar activity has been observed in other mammals. This review is the first synthesis of studies on NMDAR antagonist-enhanced HFO, identifying gaps and urging more human research.