TY - JOUR T1 - The Effect of Chronic Treatment with Lurasidone on Rat Liver Cytochrome P450 Expression and Activity in the Chronic Mild Stress Model of Depression JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1336 LP - 1344 DO - 10.1124/dmd.117.077826 VL - 45 IS - 12 AU - Marta Kot AU - Anna Haduch AU - Mariusz Papp AU - Władysława A. Daniel Y1 - 2017/12/01 UR - http://dmd.aspetjournals.org/content/45/12/1336.abstract N2 - Recent studies indicated an important role of the monoaminergic nervous systems (dopaminergic, noradrenergic, and serotonergic systems) and stress in the regulation of cytochrome P450 (CYP) expression and activity in the liver. The aim of our present research was to determine the effect of the novel atypical neuroleptic drug with antidepressant properties lurasidone, on the expression (mRNA and protein level) and activity of liver CYP isoforms involved in the metabolism of drugs and endogenous steroids, in the chronic mild stress (CMS) model of depression. Male Wistar rats were subjected to CMS for 7 weeks. Lurasidone (3 mg/kg per os per day) was administered to nonstressed or stressed animals for 5 weeks (weeks 3–7 of CMS). It has been found that 1) CMS moderately affects CYP (CYP2B, CYP2C11, and CYP3A), and its effects are different from those observed after other kinds of psychologic stress, such as repeated restraint stress or early-life maternal deprivation; 2) chronic lurasidone influences the expression and/or activity of CYP2B, CYP2C11, and CYP3A isoforms; and 3) CMS modifies the action of lurasidone on CYP expression and function, leading to different effects of the neuroleptic in nonstressed and stressed rats. Based on the obtained results, it can be suggested that the metabolism of endogenous substrates (e.g., steroids) and drugs, catalyzed by the isoforms CYP2B, CYP2C11, or CYP3A, may proceed at a different rate in the two groups of animals (nonstressed and stressed) in the rat CMS model. ER -