Molecular Psychiatry
June 1, 2026
Charles F Zorumski, Joseph Cichon, Yukitoshi Izumi et al.
5 citations
The success of ketamine, a dissociative anesthetic and non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, as a rapidly acting antidepressant has ignited efforts to identify other novel depression treatments. In recent years, several clinical trials indicated that nitrous oxide (N2O), an inhalational dissociative anesthetic in clinical use for over 150 years, also has rapid and...
Nature Communications
April 3, 2025
Joseph Cichon, Thomas Joseph, Xinguo Lu et al.
Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a stress-associated...
medRxiv : the preprint server for health sciences
August 17, 2024
Charles R Conway, Ben Julian A Palanca, Thomas Zeffiro et al.
preprint
While nitrous oxide (N2O) has demonstrated antidepressant properties in treatment-resistant major depression (TRD), little is known about neural mechanisms mediating these effects. Employing serial resting-state functional magnetic resonance imaging (rs-fMRI), we compared spatiotemporal effects of inhaled N2O on brain functional connectivity in TRD patients (n=14) and non-depressed healthy...
Biological Psychiatry
June 1, 2022
Yukitoshi Izumi, F. Hsu, C. Conway et al.
BACKGROUND: Nitrous oxide (N2O) is a non-competitive inhibitor of NMDA receptors (NMDARs) that appears to have ketamine-like rapid antidepressant effects in patients with treatment resistant major depression. In preclinical studies, ketamine enhances glutamate-mediated synaptic transmission in hippocampus and prefrontal cortex. The present study examined effects of N2O on glutamate transmission...
Journal of Neuroscience
November 2, 2016
Charles F Zorumski, Yukitoshi Izumi, Steven Mennerick
252 citations
Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the...
Frontiers in Psychiatry
2015
Charles F Zorumski, Peter Nagele, Steven Mennerick et al.
Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15-30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have...
Joseph Cichon, Thomas Joseph, Xinguo Lu et al.
Abstract Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a...