The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
Effects of prolonged antipsychotic administration on neuregulin-1/ErbB signaling in rat prefrontal cortex and myocardium: implications for the therapeutic action and cardiac adverse effect
Ruili DangYujin GuoHualin CaiRanyao YangDonglou LiangChuanfeng LvPei Jiang
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2016 Volume 41 Issue 2 Pages 303-309


Patients with schizophrenia (SCZ) are at higher risk for developing cardiovascular disease (CVD) and neuregulin-1 (NRG1)/ErbB signaling has been identified as a common susceptibility pathway for the comorbidity. Antipsychotic treatment can change NRG1/ErbB signaling in the brain, which has been implicated in their therapeutic actions, whereas the drug-induced alterations of NRG1/ErbB pathway in cardiovascular system might be associated with the prominent cardiac side-effects of antipsychotic medication. To test this hypothesis, we examined NRG1/ErbB system in rat prefrontal cortex (PFC) and myocardium following 4-week intraperitoneal administration of haloperidol, risperidone or clozapine. Generally, the antipsychotics significantly enhanced NRG1/ErbB signaling with increased expression of NRG1 and phosphorylation of ErbB4 and ErbB2 in the brain and myocardium, except that clozapine partly blocked the cardiac NRG1/ErbB2 activation, which could be associated with its more severe cardiac adverse actions. Combined, our data firstly showed evidence of the effect of antipsychotic exposure on myocardial NRG1/ErbB signaling, along with the activated NRG1/ErbB system in brain, providing a potential link between the therapeutic actions and cardiotoxicity.

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© 2016 The Japanese Society of Toxicology
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