• Chao Deng, Bo Pan, Chang-Hua Hu, Mei Han, and Xu-Feng Huang.
• Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia; Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia; Schizophrenia Research Institute, 384 Victoria Street, Darlinghurst, NSW, Australia. Electronic address: chao@uow.edu.au.
• Psychiatry Res. 2015 Feb 28;225(3):347-54.

AbstractNeuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short- or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40 kDa in the PFC and Cg was also down-regulated by olanzapine. These results suggest that the time-dependent and region-specific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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