title: The depressogenic-like effect of acute and chronic treatment with dexamethasone and its influence on the activity of antidepressant drugs in the forced swim test in adult mice.
abstract: There is a close relationship between chronic stress, glucocorticoids and depression. Psychiatric and cognitive symptoms resembling major depression have been observed in patients experiencing elevated glucocorticoid levels, and a high percentage of people suffering from depression have undergone a stressful event/events prior to the onset of this mental disorder. In our study, we investigated whether acute and chronic treatment of dexamethasone induces depression-like behavior in mice and if dexamethasone therapy influences the activity of antidepressant drugs with diverse modes of action. The antidepressant-like effect was assessed by the forced swim test in adult mice. The depressogenic-like activity of dexamethasone turned out to be dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64μg/kg) given as a single injection increased immobility time, whereas 16μg/kg/day of dexamethasone (but not 4μg/kg/day) administered repeatedly induced a significant alteration in animal behavior. These depressogenic doses of dexamethasone (i.e., 64μg/kg and 16μg/kg/day for an acute and repeated administration, respectively) diminished the antidepressant potential of the therapeutic doses of imipramine (10mg/kg), amitriptyline (10mg/kg), tianeptine (25mg/kg), mianserin (10mg/kg), citalopram (15mg/kg) and moclobemide (25mg/kg). Two main findings of our study should be particularly underlined: (1) both single and repeated administration of dexamethasone evoked a depression-like behavior of mice, (2) both single and repeated administration of dexamethasone were able to modify the activity of the antidepressant agents from various pharmacological groups, which may lead to a considerable reduction in the efficacy of pharmacotherapy prescribed for patients with mood disorders.
authors.affiliation: Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wróbel
authors.affiliation: Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093 Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Serefko
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
authors.affiliation: Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093 Lublin, Poland. Electronic address: ewa.poleszak@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D020912:Moclobemide / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D013550:Swimming; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D005938:Glucocorticoids; D013841:Thiazepines; D015283:Citalopram; C050504:tianeptine; D000639:Amitriptyline; D008803:Mianserin; D003907:Dexamethasone; D007099:Imipramine; D020912:Moclobemide
keywords: Antidepressant-like activity; Dexamethasone; Forced swim test; Mice