(R)-ketamine attenuates neurodevelopmental disease-related phenotypes in a mouse model of maternal immune activation.
Elifrances Galdino de Oliveira, Diógenes Afonso De Lima, José Carlos Da Silva Júnior, Mayara Victória De Souza Barbosa, Severina Cassia De Andrade Silva, Jonata Henrique De Santana, Osmar Henrique Dos Santos Júnior, Eduardo Carvalho Lira, Claudia Jacques Lagranha, Filipe Silveira Duarte, Dayane Aparecida Gomes
European Archives of Psychiatry and Clinical Neuroscience October 2023 DOI: 10.1007/s00406-023-01629-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Male offspring of Swiss mice exposed to maternal immune activation via lipopolysaccharide |
| Interventions | (R)-ketamine lipopolysaccharide |
| Dose | 20 mg/kg/day (R)-ketamine; 100 µg/kg/day lipopolysaccharide |
| Duration | (R)-ketamine from postnatal day 36 to 50; behavioral testing at PND 62; tissue collection at PND 63 |
| Measures | open-field test (OFT), social interaction test (SIT), lipid peroxidation, gene expression of IL-1β, IL-6, TGF-β1 |
| Topics | Ketamine Esketamine |
| Keywords | Emotional behavior Inflammation Maternal immune activation Oxidative imbalance Prefrontal cortex |
| Key findings | (R)-ketamine administered during adolescence abolished anxiety-related behavior and social interaction deficits in male offspring exposed to maternal immune activation, and attenuated increases in lipid peroxidation and prefrontal cortex cytokines IL-1β, IL-6, and TGF-β1. The authors suggest these lasting behavioral effects may stem from antioxidant and anti-inflammatory activity in the prefrontal cortex. |
Abstract
Infections during pregnancy are associated with an increased risk of neuropsychiatric disorders with developmental etiologies, such as schizophrenia and autism spectrum disorders (ASD). Studies have shown that the animal model of maternal immune activation (MIA) reproduces a wide range of phenotypes relevant to the study of neurodevelopmental disorders. Emerging evidence shows that (R)-ketamine attenuates behavioral, cellular, and molecular changes observed in animal models of neuropsychiatric disorders. Here, we investigate whether (R)-ketamine administration during adolescence attenuates some of the phenotypes related to neurodevelopmental disorders in an animal model of MIA. For MIA, pregnant Swiss mice received intraperitoneally (i.p.) lipopolysaccharide (LPS; 100 µg/kg/day) or saline on gestational days 15 and 16. The two MIA-based groups of male offspring received (R)-ketamine (20 mg/kg/day; i.p.) or saline from postnatal day (PND) 36 to 50. At PND 62, the animals were examined for anxiety-like behavior and locomotor activity in the open-field test (OFT), as well as in the social interaction test (SIT). At PND 63, the prefrontal cortex (PFC) was collected for analysis of oxidative balance and gene expression of the cytokines IL-1β, IL-6, and TGF-β1. We show that (R)-ketamine abolishes anxiety-related behavior and social interaction deficits induced by MIA. Additionally, (R)-ketamine attenuated the increase in lipid peroxidation and the cytokines in the PFC of the offspring exposed to MIA. The present work suggests that (R)-ketamine administration may have a long-lasting attenuation in deficits in emotional behavior induced by MIA, and that these effects may be attributed to its antioxidant and anti-inflammatory activity in the PFC.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Understanding the role of the NMDA receptor subunit, GluN2D, in mediating NMDA receptor antagonist-induced behavioral disruptions in male and female mice. Journal of Neuroscience Research 2024
- Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target? Molecular Neurobiology February 5, 2026
- Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum. Psychopharmacology November 28, 2025
Cites 10
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