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.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Han J,Wang G,Liu M,Chai R,Guo J,Zhang F,Lu C,Zhang Y,Wang H,Zhang Rdoi
10.1016/j.bbr.2020.112561subject
Has Abstractpub_date
2020-05-15 00:00:00pages
112561eissn
0166-4328issn
1872-7549pii
S0166-4328(19)31257-4journal_volume
385pub_type
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