Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.

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.