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 via PubMed
Summary
AI-generated from the abstractInhaling 50% nitrous oxide for one hour and a single low dose of ketamine both alter the activity of genes that regulate mitogen-activated protein kinases in the medial prefrontal cortex of adult mice, particularly in pyramidal cells. Nitrous oxide produced much larger and more widespread changes in gene expression than ketamine. Ketamine increased the firing rate of putative pyramidal neurons and boosted gamma brain wave activity, whereas nitrous oxide did not. The findings suggest that the two drugs share a common molecular target but cause different immediate electrical changes in the brain.
Study at a glance
| 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 |
| Keywords | Medial prefrontal cortex Nitrous oxide Single-unit activity |
| Key finding | 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.