Nitrous oxide promotes exploratory activity and stimulates neurogenesis in a male rat model of post-traumatic stress disorder.
Batoul Darwish, Jad El Masri, Lina Hourieh, Ziad Nahas, Wassim Abou-Kheir, Farah Chamaa
Neuroscience January 26, 2026 DOI: 10.1016/j.neuroscience.2025.12.017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male rats |
| Intervention | Nitrous oxide gas |
| Topics | Neuroplasticity PTSD |
| Keywords | Hippocampus Nitrous oxide n2o Psychological disorders |
| Key points | Nitrous oxide exposure reduced anxiety-related symptoms and enhanced hippocampal neurogenesis in rats with PTSD-like behavior induced by single prolonged stress. |
Abstract
Neurogenesis in the adult brain is a precisely regulated process that remains highly sensitive to intrinsic and extrinsic influences. Among the external factors are psychological conditions, such as post-traumatic stress disorder (PTSD), which arises after exposure to trauma such as war, accidents, violence, or natural disasters. PTSD, as well as other disorders like stress and depression, has been linked to diminished hippocampal neurogenesis. In this study, we utilized the single prolonged stress (SPS) model to induce PTSD-like behavior in male rats, demonstrating its suppressive effects on hippocampal neurogenesis and on exploratory behavior. Recent research has explored the potential of nitrous oxide gas (N2O), an anesthetic and analgesic used in medical procedures, as a potential treatment for depression. Accordingly, we propose nitrous oxide exposure as a therapeutic intervention for PTSD-like to counteract its adverse effects on neurogenesis and anxiety-related behavior. Our results showed that SPS-exposed rats exhibited reduced exploratory performance in the Y-maze test and increased anxiety behavior in the elevated plus maze. Furthermore, BrdU tracing revealed decreased neurogenesis in these rats compared to sham. Remarkably, exposure to nitrous oxide reduced anxiety-related symptoms of SPS-exposed rats and enhanced neurogenesis. This aligns with prior research, highlighting nitrous oxide as a promising therapeutic avenue for addressing PTSD and other psychological disorders. We propose nitrous oxide as a therapeutic approach for treating cognitive and anxiety-related symptoms of PTSD through its effects on hippocampal neurogenesis. However, further comprehensive research is essential to understand the potential benefits, risks and long-term impacts associated with this treatment approach.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cites 11
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD. Translational Psychiatry May 25, 2024
- Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect. Nature Communications April 3, 2025
- Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. PLoS One 2024
and 6 more in the library