Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex.
Wei Liu, Qian Li, Binglu Ye, Hang Cao, Fuyi Shen, Zhendong Xu, Weijia Du, Fei Guo, Jinqi Liu, Tianyu Li, Bing Zhang, Zhiqiang Liu
Frontiers in Psychiatry 2020 DOI: 10.3389/fpsyt.2020.00837 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Topics | Depression |
| Keywords | Bdnf Burst firing Mpfc Nitrous oxide n2o |
| Key points | Repeated N2O exposure produces antidepressant-like effects in mice by increasing BDNF expression and burst firing rates through activation of nNOS in the mPFC. |
Abstract
Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (N2O) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of N2O remain largely unknown. Neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of N2O. In this study, we revealed that repeated N2O exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated N2O exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of N2O were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that N2O exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of N2O exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of N2O.
Comparable studies
Other preclinical and animal studies on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... | 2011 | Animal experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study |
Citations in the library
Cited by 14
- The role of neurotrophic factors in novel, rapid psychiatric treatments. Neuropsychopharmacology 2024
- Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry Pharmacopsychiatry January 19, 2022
- Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care. Anesthesiology August 1, 2024
- Anesthetics as Treatments for Depression: Clinical Insights and Underlying Mechanisms. Annual Review of Neuroscience February 19, 2025
- Rapid antidepressant potential of nitrous oxide: current state and major questions. Molecular Psychiatry June 1, 2026
and 9 more in the library
Cites 10
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine The International Journal of Neuropsychopharmacology November 14, 2017
- Exploring Nitrous Oxide as Treatment of Mood Disorders: Basic Concepts. Journal of Clinical Psychopharmacology April 1, 2018
and 5 more in the library