Chronic Antipsychotic Drugs Administration Alters The Expression Of NRG1, ErbB2, ErbB3 And ErbB4 In Rat Prefrontal Cortex And Hippocampus

NRG1 (Neuregulin 1) has been identified as a leading susceptibility gene for schizophrenia, and dysregulation of NRG1 and its ErbB receptors are implicated in the pathophysiology of the disorder.Antipsychotic drugs can substantially improve the symptoms of schizophrenia, but it always takes weeks to exhibit their full therapeutic effects. Recently it has been suggested that the molecular and cellular adaptations following repeated antipsychotic drugs administration contribute to their mechanisms of action.Based on previous studies indicating that antipsychotic drugs alter NRG1-ErbB signaling, we evaluated the immunoreactivity of NRG1βand ErbB4 in rat hippocampus after chronic treatment of antipsychotic drugs and an NMDA receptor antagonist MK-801 using immunohistochemistry. According to the preliminary results, we further examined the protein expression levels of NRG1β, ErbB2, ErbB3 and ErbB4 in rat prefrontal cortex and hippocampus following 4 weeks administration of haloperidol (1 mg/kg, i.p.), clozapine (10 mg/kg, i.p.) or risperidone (1 mg/kg, i.p.) by using immunohistochemistry and Western blot.The results of this study showed that haloperidol promoted the expression of NRG1βand ErbB4 whereas clozapine inhibited NRG1βexpression in rat prefrontal cortex. Both haloperidol and clozapine significantly increased the protein levels of NRG1βand ErbB receptors in rat hippocampus. Repeated administration of risperidone only increased the expression of NRG1βand ErbB4 in the hippocampus.Our findings demonstrate that antipsychotic drugs differentially alter the expression of NRG1 and ErbB receptors in rat prefrontal cortex and hippocampus, which may help to elucidate the molecular basis of the therapeutic effects of antipsychotic drugs and provide insights into the treatment and pathophysiology of schizophrenia.