bioRxiv Preprint Server
September 19, 2022
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
preprint
Inhaling 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.
Neuropharmacology
December 15, 2024
Okko Alitalo, Samuel Kohtala, Marko Rosenholm et al.
A brief exposure to nitrous oxide (N2O) causes a drop in body temperature, reduced movement, enhanced slow-wave brain activity, decreased brain glucose use, and increased phosphorylation of TrkB, GSK3β, and p70S6K in the medial prefrontal cortex of adult male mice. Preventing the hypothermic response in a chronic stress model of depression weakened the antidepressant-like behavioral effects of N2O in the saccharin preference test. These findings indicate that N2O treatment modulates TrkB signaling and related neurotrophic pathways in a temperature-dependent manner, linking altered thermoregulation and energy expenditure to antidepressant-like behavioral responses.
European journal of pharmacology
April 5, 2024
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
Inhaling 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.
bioRxiv
August 31, 2021
O. Alitalo, S. Kohtala, Marko Rosenholm et al.
preprint
Both pharmacological and non-pharmacological treatments for depression activate TrkB receptors—a known antidepressant target—by inducing a physiological response linked to sedation. Rapid-acting antidepressants trigger TrkB signaling by evoking a state characterized by electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. This signaling was not impaired in animals with reduced activity-dependent BDNF release but was diminished by maintaining animals in a warm ambient temperature. Preventing the hypothermic response attenuated the behavioral effects of the rapid-acting antidepressant nitrous oxide. The findings suggest that changes in energy expenditure and thermoregulation are essential, but not sufficient, for antidepressant responses, challenging pharmacology-centric hypotheses and highlighting the role of bioenergetics and thermoregulation.