Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus.
Farah Chamaa, Hisham F Bahmad, Ahmad-Kareem Makkawi, Reda M Chalhoub, Elie D Al-Chaer, George B Bikhazi, Ziad Nahas, Wassim Abou-Kheir
Frontiers in Cellular Neuroscience 2018 DOI: 10.3389/fncel.2018.00135 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Intervention | Nitrous oxide (N2O) |
| Dose | 70% N2O and 30% oxygen |
| Duration | Single or multiple exposures; assessed at day 1 and day 7 |
| Measures | BrdU incorporation, BrdU-positive cell counts in dentate gyrus |
| Topics | Depression Neuroplasticity |
| Keywords | Anesthetics Dentate gyrus Hippocampus Nitrous oxide |
| Key points | Sub-anesthetic doses of nitrous oxide increase hippocampal cell proliferation in adult male rats, with a 1.4-fold increase after single exposure at day 7 and a two-fold increase after multiple exposures. |
Abstract
The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N2O) is an N-methyl-D-aspartic acid (NMDA) antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD) patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N2O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N2O and 30% oxygen (O2). Sham groups were exposed to 30% O2 and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG) using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N2O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N2O. Multiple N2O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N2O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N2O exposures and their antidepressant behavioral correlates.
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
Cited by 4
- Nitrous oxide promotes exploratory activity and stimulates neurogenesis in a male rat model of post-traumatic stress disorder. Neuroscience January 26, 2026
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook. Frontiers in Psychiatry 2025
- Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study. Molecular Psychiatry September 1, 2023
- Ketamine and nitrous oxide: The evolution of NMDA receptor antagonists as antidepressant agents. Journal of the Neurological Sciences May 15, 2020
Cites 8
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- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
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and 3 more in the library