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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.

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