Sabinene's neuroprotective effect reverses ketamine-induced experimental schizophrenia in mice through enhancement of cholinergic, antioxidant, and anti-inflammatory mechanisms.
Lydia Ben-Azu, Onyeka B Onyeukwu, Bienose S Chijioke, Maxwell Oboh, Daniel T Esuku, Paul Adeleke, Jackson E Onuelu, Benneth Ben-Azu
Journal of Psychiatric Research March 5, 2026 DOI: 10.1016/j.jpsychires.2026.02.055 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Male mice with ketamine-induced schizophrenia-like deficits |
| Interventions | Sabinene Risperidone Ketamine |
| Dose | Sabinene 5 or 10 mg/kg, p.o.; risperidone 0.5 mg/kg, p.o.; ketamine 20 mg/kg/day, i.p. |
| Duration | Ketamine for 14 days; sabinene or risperidone from days 8-14 |
| Measures | Superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), thiobarbituric acid-reactive substance (TBARS), nitrite, acetylcholinesterase activity, IL-6, IL-10 |
| Topics | Ketamine Esketamine |
| Keywords | Hippocampus Prefrontal cortex Animals Mice Disease models, animal Neuroprotective agents Anti-inflammatory agents Antioxidants Schizophrenia Oxidative stress Male Oxidative damage Neuroprotection Psychosis Cholinergic dysfunction Sabinene |
| Key findings | Sabinene at 10 mg/kg, comparable to risperidone, reversed ketamine-induced hyperactivity, social withdrawal, and memory impairment in mice and normalized oxidative stress markers, cytokines (IL-6, IL-10), and acetylcholinesterase activity across prefrontal cortex, striatum, and hippocampus; the 5 mg/kg dose showed limited efficacy, indicating dose-dependency. The authors suggest sabinene's effects involve cholinergic enhancement and inhibition of oxidative, nitrergic, and inflammatory processes. |
Abstract
Schizophrenia is a serious neuropsychiatric disorder marked by oxidative stress, immune system changes, and neurochemical imbalances. Current treatments are constrained by inconsistent effectiveness and side effects. This study evaluates the neuroprotective effects of sabinene, a monoterpene, in a mouse model of ketamine-induced schizophrenia. Male mice received ketamine (20 mg/kg/day, i.p.) for 14 days to induce schizophrenia-like deficits, followed by treatment with sabinene (5 or 10 mg/kg, p.o.) or risperidone (0.5 mg/kg, p.o.) from days 8-14. Neurochemical analyses assessed oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), thiobarbituric acid-reactive substance (TBARS), and nitrite. This was followed by assays of acetylcholinesterase activity and levels of cytokines (IL-6 and IL-10) in the prefrontal cortex, striatum, and hippocampus. Ketamine-induced hyperactivity, social withdrawal and memory impairment compared to the ketamine group, which were reversed by sabinene. Sabinene (10 mg/kg) and risperidone restored SOD, GST, and CAT activities, GSH concentration, and reduced TBARS and nitrite concentrations across regions. The increased IL6 and reduced IL-10 levels by ketamine were reversed by sabinene in the prefrontal cortex, striatum, and hippocampus compared to the ketamine groups. Sabinene (10 mg/kg) also attenuated acetylcholinesterase activity in the prefrontal cortex and hippocampus. The 5 mg/kg dose showed limited efficacy, indicating dose-dependency. Sabinene's efficacy, comparable to risperidone, involves enhancement of the cholinergic system and inhibition of oxidative/nitrergic stress and brain inflammation, suggesting its potential as a therapeutic agent for schizophrenia by improving cholinergic transmission deficits. Further mechanistic and clinical studies are warranted to optimize sabinene's therapeutic benefits and antipsychotic-like potential.
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
Cites 11
- Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase Science December 6, 2007
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- 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
- Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia. Journal of Neuroimmune Pharmacology July 3, 2025
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