Antipsychotic Potential of Quinazoline ErbB1 Inhibitors in a Schizophrenia Model Established With Neonatal Hippocampal Lesioning

摘要: Abstract. Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in pathophysiology schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 – 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In present study, we used an animal model schizophrenia established by neonatal hippocampal lesioning evaluated neurobehavioral consequences ErbB1-inhibitor Subchronic administration inhibitor ZD1839 to cerebroventricle rats receiving ameliorated deficits prepulse inhibition well those latent tone-dependent fear learning. There were no apparent adverse effects on basal learning scores locomotor activity, however. The other inhibitors, PD153035 OSI-774, similarly attenuated impairment this model. parallel, there decreases phosphorylation animals treated with inhibitors. These results indicate potential ErbB tyrosine kinases may novel therapeutic targets its related psychotic symptoms.