Dizocilpine induced psychosis-like behavior in rats: A possible animal model with full spectrum of schizophrenia

Abstract

Schizophrenia (SZ) is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate (NMDA) receptor antagonist known to induce hyperlocomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats (100-150g) at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test (SPT) and social interaction test (SIT). Moreover, Cognitive deficits were evaluated by novel object recognition test (NORT). After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation (LPO) in brain and a decline in reduced glutathione (GSH) levels. Biogenic amine levels (Dopamine, DA; 5-hydroxytryptamine, 5-HT) were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study.