Abstract

Reduced Neuregulin 1 Expression in the Medial Prefrontal Cortex of a Rat Ketamine Model for Schizophrenia

Author(s): Quan-Chi Moa, Jin-Chung Chen

Chronic consumption of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (KET) induces positive, negative and cognitive deficits in humans which closely resemble symptoms in schizophrenic patients. Human genetic analyses has revealed that neuregulin 1 (NRG1) and its receptor ErbB are Schizophrenia-related genes in some schizophrenic patients. Male SD rats were injected daily with 30 mg/kg KET for five consecutive days to investigate if the KET-induced behavioral abnormality was linked with an alternation of brain NRG1. The KET-treated rats exhibited locomotor/stereotypy up-regulation and a defect in sensorimotor gating, resembling the behavioral phenotype of schizophrenia. Antipsychotics were administered to KET-treated rats to pharmacologically validate this animal model. Clozapine, but not haloperidol or sulpride rescued pre-pulse inhibition (PPI) dysfunction only when coadministered with KET and not following pre-treatment with KET. NRG1 protein levels were progressively decreased in the medial prefrontal cortex, but not the ventral striatum of KETtreated rats during the withdrawal period of up to two weeks. On the other hand, ErbB2, ErbB3 and ErbB4 levels were unchanged in these two brain areas. These results suggest that KETinduced schizophrenia-like symptoms might be linked with abnormal NRG1 expression in the medial prefrontal cortex.