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Kososan, but not milnacipran, elicits antidepressant‐like effects in a novel psychological stress‐induced mouse model of depression
Author(s) -
Hori Atsushi,
Ito Naoki,
Oikawa Tetsuro,
Hanawa Toshihiko
Publication year - 2015
Publication title -
traditional and kampo medicine
Language(s) - English
Resource type - Journals
ISSN - 2053-4515
DOI - 10.1002/tkm2.1013
Subject(s) - milnacipran , behavioural despair test , antidepressant , open field , medicine , endocrinology , bromodeoxyuridine , corticosterone , psychology , depression (economics) , animal models of depression , hormone , hippocampus , immunohistochemistry , macroeconomics , economics
Aim Mild or moderate depressive symptoms are often resistant to treatment with currently available antidepressants. We constructed a novel animal model of depression induced by the exposure of mice to psychological stress and evaluated the antidepressant efficacy of kososan and milnacipran. Methods Depressive state was elicited in mice by repeated rat‐exposure stress over 10 days. Kososan or milnacipran were administered orally during the stress paradigm. Alterations in behavioral indices (evaluated using forced swimming test and open‐field test), cell proliferation (evaluated on bromodeoxyuridine immunohistochemistry), and orexin‐A production were evaluated. Results Mice exposed to psychological stress had increased immobility time on forced swimming test, and elevated serum corticosterone. Additionally, decreased bodyweight gain during the stress exposure and reduced food or water intake following the stress were observed. Although oral kososan improved the immobility time on forced swimming test without affecting the locomotor activity in open‐field test, treatment with milnacipran did not alter the immobility time. The number of cells staining positive for bromodeoxyuridine in the dentate gyrus or for orexin‐A in the lateral hypothalamic area was not affected by the stress exposure. Conclusion Psychological stress‐induced mouse model of depression was successfully implemented, with animals exhibiting symptoms of mild or moderate depressive state. This model differs from previous physical stress‐based models, as evidenced by bromodeoxyuridine or orexin‐A staining. Kososan, but not milnacipran, was found to elicit antidepressant‐like effects in this model.