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×11days). 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.
Möller
Marisa
M
Unit for Drug Research and Development, Division of Pharmacology, School of Pharmacy, North West University, Potchefstroom, South Africa.
Du Preez
Jan L
JL
Emsley
Robin
R
Harvey
Brian H
BH
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D007398:Interpersonal Relations; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000502:physiology*; D012934:Social Isolation / Q000523:psychology*; D013997:Time Factors
D014150:Antipsychotic Agents; D003024:Clozapine