Geraniol, a natural compound, prevented and reversed schizophrenia-like behaviors—hyperactivity, impaired spatial memory, and social withdrawal—induced by ketamine in male Swiss mice. It restored antioxidant defenses (glutathione, superoxide dismutase, catalase), reduced oxidative damage (malondialdehyde, nitrite), and lowered inflammatory cytokines (TNF-α, IL-6) in the striatum, prefrontal cortex, and hippocampus. Geraniol also suppressed expression of NF-κB, COX-2, and iNOS proteins in those brain regions. The findings suggest geraniol has neuroprotective and neurorestorative effects against schizophrenia-like symptoms by counteracting oxidative stress and neuroinflammation.
Fluvoxamine, a sigma-1 receptor agonist, alleviated learning deficits, cognitive inflexibility, and social impairments in a rat model of schizophrenia induced by ketamine. It restored nNOS/PSD-95/NMDAR signaling, increased parvalbumin and GAD67 levels in the prefrontal cortex, and reduced markers of unfolded protein response (IRE-1, PERK, ATF-6), indicating relief from ER stress. Fluvoxamine also lowered inflammatory markers (Iba-1, TNF-α) and apoptotic markers (Bax, caspase-12) while increasing Bcl-2, and reduced neuronal damage. Co-administration of the sigma-1 receptor blocker NE100 diminished these effects, implicating sigma-1 receptor signaling as a therapeutic target for schizophrenia.