Effects of nitrous oxide and ketamine on the prefrontal cortex in mice: a comparative study
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug, Markus Storvik, Claudio Rivera, Tomi Rantamäki
bioRxiv Preprint Server September 19, 2022 preprint DOI: 10.1101/2022.09.19.508563 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study |
|---|---|
| Population | Adult mice |
| Interventions | Nitrous oxide Ketamine |
| Dose | 50% N2O for 1 h; single subanesthetic dose of ketamine |
| Duration | 1-hour inhalation for N2O; single dose for ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Antidepressant research Depression treatment Mental health Psychiatric research Therapeutic potential Brain science Neurobiology Brain function Neural activity Brain mechanisms Drug action Psychopharmacology Drug mechanisms Nitrous oxide Molecular mechanisms Gene expression Genetic impacts Cellular pathways Brain cell regulation Genomics |
| Key findings | Nitrous oxide and ketamine both alter transcription of MAPK regulators in the medial prefrontal cortex, but nitrous oxide produces more widespread gene expression changes without increasing neuronal firing or gamma activity. |
Abstract
Nitrous oxide (N2O; laughing gas) has recently been reported as a putative rapid-acting antidepressant, 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 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. 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. Thus, this study characterized the electrophysiological and transcriptome-wide changes in mPFC triggered by exposure to N2O and compared them with those caused by the rapid-acting antidepressant ketamine in terms of both the direction of their regulation and localization.
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
Cites 7
- 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
- Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex. Frontiers in Psychiatry 2020
- Cortical Excitability and Activation of TrkB Signaling During Rebound Slow Oscillations Are Critical for Rapid Antidepressant Responses. Molecular Neurobiology June 1, 2019
and 2 more in the library