title: Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain.
abstract: Neuregulin-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.
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia; Institute of Modern Biopharmaceuticals, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing, People׳s Republic of China.
authors.forename: Chang-Hua
authors.initials: CH
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020890:Neuregulin-1 / Q000378:metabolism*; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D020890:Neuregulin-1; D010879:Piperazines; D015363:Quinolones; D001569:Benzodiazepines; D000068180:Aripiprazole; D066247:Receptor, ErbB-4; D006220:Haloperidol; D000077152:Olanzapine
keywords: Antipsychotic; Aripiprazole; ErbB4 receptor; Haloperidol; Neuregulin-1; Olanzapine