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.
Unit for Drug Research and Development, Division of Pharmacology, School of Pharmacy, North West University, Potchefstroom, South Africa.
Marisa
M
Möller
Jan L
JL
Du Preez
Robin
R
Emsley
Brian H
BH
Harvey
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