Effects of quetiapine on behavioral changes and expression of myelin proteins in a chronic alcohol dependence rat model

Abstract Background As an atypical antipsychotic drug, quetiapine had been approved for bipolar disorder and for adjunctive therapy in major depressive disorder and schizophrenia. Recently quetiapine has been suggested to be a promising pharmacotherapy for alcohol dependence. This study was performed to determine the effects of quetiapine in rats chronically exposed to ethanol. Methods Rats were exposed to ethanol solution (10 %; v/v) for 6 weeks. Saline or one of three doses of quetiapine (10, 20 or 40 mg/kg/day) was given by oral gavage while ethanol exposure for the next 14 weeks. Performance of learning and memory and withdrawal signs were evaluated. Then immunohistochemistry, western blot, quantitative real-time-PCR and transmission electron microscopy were performed to determine the effects of quetiapine on alterations of brain white matter markers (myelin basic protein, MBP; proteolipid protein, PLP) and morphology caused by chronic ethanol exposure. Results Quetiapine treatment significantly alleviated withdrawal signs in the ethanol exposed rats. Chronic ethanol exposure reduced Y-type electric maze scores and the protein/mRNA expression levels of MBP and PLP in the prefrontal cortex and hippocampus, and these effects were reversed by quetiapine treatment. Similar ultrastructure morphological changes were observed. Conclusions Chronic quetiapine treatment alleviated the damage induced by chronic ethanol exposure with regard to learning and memory ability and to brain white matter. Thus, quetiapine appears to be a potentially promising pharmacotherapy for the treatment of alcohol use disorder.