Effects of nitrous oxide and ketamine on electrophysiological and molecular responses in the prefrontal cortex of mice: A comparative study.
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug, Markus Storvik, Claudio Rivera, Tomi Rantamäki
European Journal of Pharmacology April 5, 2024 DOI: 10.1016/j.ejphar.2024.176426 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult mice |
| Interventions | Nitrous oxide Ketamine |
| Dose | 50% N2O for 1 h; 10 mg/kg ketamine i.p. |
| Duration | 1-hour inhalation for N2O; single injection for ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Medial prefrontal cortex Nitrous oxide Single-unit activity |
| Key findings | Nitrous oxide and subanesthetic-dose ketamine both affect the transcription of dual specificity phosphatases in the medial prefrontal cortex, but produce different acute electrophysiological responses. |
Abstract
Nitrous oxide (N2O; laughing gas) has recently reported to produce rapid antidepressant effects, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N2O and a single subanesthetic dose of ketamine (10 mg/kg, i.p.) in the medial prefrontal cortex (mPFC) in adult mice. Both treatments similarly affected the transcription of several negative regulators of mitogen-activated protein kinases (MAPKs), namely, dual specificity phosphatases (DUSPs). The effects were primarily located in the pyramidal cells. Notably, the overall effects of N2O on mRNA expression were much more prominent and widespread compared to ketamine. Ketamine caused an elevation of the spiking frequency of putative pyramidal neurons and increased gamma activity (30-100 Hz) of cortical local field potentials. However, N2O produced no such effects. Spiking amplitudes and spike-to-local field potential phase locking of putative pyramidal neurons and interneurons in this brain area showed no uniform changes across treatments. Our findings suggest that N2O and subanesthetic-dose ketamine target MAPK pathway in the mPFC but produce varying acute electrophysiological responses.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Rapid antidepressant potential of nitrous oxide: current state and major questions. Molecular Psychiatry June 1, 2026
- Beyond surgery: Repurposing anesthetics for treatment of central nervous system disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 20, 2025
- Nitrous oxide modulates cortical activity, wake–sleep oscillations, and produces antidepressant-like effects in mice
Cites 12
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines Nature Communications June 3, 2019
- A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression. Science Translational Medicine June 9, 2021
- Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway. Progress in Neuro-Psychopharmacology and Biological Psychiatry February 25, 2020
and 7 more in the library