Chronic antipsychotic drug administration alters the expression of neuregulin 1beta, ErbB2, ErbB3, and ErbB4 in the rat prefrontal cortex and hippocampus.

Neuregulin 1 (NRG1) has been identified as a susceptibility gene for schizophrenia, and dysregulation of NRG1 and its ErbB receptors is implicated in the pathophysiology of the disorder. The present study examined the protein expression levels of NRG1beta, ErbB2, ErbB3 and ErbB4 in the rat prefrontal cortex and hippocampus following a 4-wk 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 showed that haloperidol promoted the expression of NRG1beta and ErbB4, whereas clozapine inhibited NRG1beta expression in the rat prefrontal cortex. Both haloperidol and clozapine significantly increased the protein levels of NRG1beta and ErbB receptors in the rat hippocampus. Repeated administration of risperidone only increased the expression of NRG1beta and ErbB4 in the hippocampus. Our findings demonstrate that antipsychotic drugs differentially regulate the expression of NRG1 and ErbB receptors in the rat brain, which may provide insight into the molecular basis of the pharmacological profile of antipsychotic drugs.