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 via bioRxiv
Summary
AI-generated from the abstractInhaling 50% nitrous oxide (laughing gas) for one hour and a single low dose of ketamine both alter gene expression in the medial prefrontal cortex of adult mice, particularly affecting regulators of MAPK signaling pathways in pyramidal cells. Nitrous oxide produced much broader and more widespread changes in mRNA expression than ketamine. However, unlike ketamine, nitrous oxide did not increase the firing rate of putative pyramidal neurons or boost gamma brain wave activity. The findings suggest that while both substances share some molecular effects, their neural activity patterns differ markedly.
Study at a glance
| 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 |
| Keywords | Antidepressant research Depression treatment Mental health Psychiatric research Therapeutic potential |
| Key finding | 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.