Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.
Christian I Uruaka, Benneth Ben-Azu, Noah A. Omeiza, Emmanuel O Chidebe, Abayomi M Ajayi, Cletus B Lemii, Tamunobarabiye I Nonju, Udeme O Georgewill, Owunari A Georgewill
Journal of Neuroimmune Pharmacology July 3, 2025 DOI: 10.1007/s11481-025-10226-1 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with drug-alone, preventive, and reversal groups Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Adult male Swiss mice |
| Interventions | Geraniol Risperidone Ketamine |
| Dose | 25, 50 and 100 mg/kg/p.o./day geraniol; 0.5 mg/kg/p.o./day risperidone; 20 mg/kg/i.p./day ketamine |
| Duration | 14 days |
| Topics | Esketamine Ketamine |
| Keywords | Anti-inflammation Antioxidant Geraniol Neuroinflammation Schizophrenia |
| Citations | 6 |
| Key findings | Geraniol prevented and reversed ketamine-induced schizophrenia-like behaviors, oxidative stress, and neuroinflammation in mice. |
Abstract
Imbalances in redox and neuroinflammation are believed to play a role in the complex causes of schizophrenia, a widespread mental disorder characterized by abnormal behaviour. In this regard, we investigated the effects of geraniol, a natural compound with various medicinal uses, on ketamine-induced schizophrenia-like behaviour, oxidative stress and neuroinflammation in mice. We conducted three sets of experiments with adult male Swiss mice (n = 7): drug alone, preventive and reversal groups. The treatments included saline (10 mL/kg/p.o./day), geraniol (25, 50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) for 14 days, along with ketamine (20 mg/kg/i.p./day) injections between days 8-14 in the preventive group, or ketamine administration for full 14 days before therapeutic intervention from days 8-14 in the reversal group. We measured behavioural hyperactivity, cognition and sociability. Additionally, brain oxidative/nitrergic imbalance, inflammatory cytokines (TNF-α, IL-6) and proteins (COX-2, iNOS, NF-κB) were determined in the striatum, prefrontal cortex, and hippocampus. KET administration was associated with schizophrenia-like symptoms as characterized by increased hyperlocomotion, impaired spatial memory and social withdrawal, particularly in the reversal group. This was exacerbated by redox imbalance and neuroinflammation in specific brain regions. However, geraniol (25, 50 and 100 mg/kg) treatment significantly prevented and reversed the brain's insults by restoring ketamine-induced decreases in glutathione, superoxide-dismutase and catalase activities, reduced malondialdehyde and nitrite contents along with TNF-α and IL-6 concentrations. Geraniol also suppressed NF-κB, COX-2 and iNOS expressions in the striatum, prefrontal-cortex and hippocampus. Geraniol shows neuroprotective and neurorestorative effects against schizophrenia-like symptoms by inhibiting oxidative stress, neuroinflammatory cytokines, and protein expression in mouse brains.
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 2
- Sabinene's neuroprotective effect reverses ketamine-induced experimental schizophrenia in mice through enhancement of cholinergic, antioxidant, and anti-inflammatory mechanisms. Journal of Psychiatric Research March 5, 2026
- Chlorogenic Acid Attenuates Schizophrenia-Like Behavioral Deficits and Neuroinflammation in a Ketamine-Induced Mouse Model
Cites 9
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase Science December 6, 2007
- Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways Journal of Psychopharmacology September 17, 2013
- Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action. Journal of Psychiatric Research November 1, 2024
- Sex-Dependent Attentional Impairments in a Subchronic Ketamine Mouse Model for Schizophrenia Biological Psychiatry Global Open Science May 29, 2023
and 4 more in the library