Isolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration

Social isolation rearing (SIR) in rats induces behavioral and glutamatergic changes akin to schizophrenia. We studied the effects of 8 weeks SIR on cortico-striatal redox and social and cognitive behaviors in rats. SIR increased superoxide dismutase activity, decreased oxidized:reduced glutathione ratio and increased lipid peroxidation in both brain regions, and induced deficits in prepulse inhibition and social and self-directed interactive behaviors. Both behavioral and cortico-striatal redox disturbances were corrected by clozapine (5 mg/kg/day × 11 days). Behavioral changes evoked by SIR are associated with cortico-striatal oxidative stress that is reversed by clozapine treatment, providing novel insight into the neurobiology and treatment of schizophrenia.