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.
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| 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.
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| Authors | Andrzej Wróbel, Anna Serefko, Piotr Wlaź, Ewa Poleszak |
| Journal | Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 54 Pg. 243-8 (Oct 03 2014) ISSN: 1878-4216 [Electronic] England |
| PMID | 24984273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
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