Kososan, but not milnacipran, elicits antidepressant‐like effects in a novel psychological stress‐induced mouse model of depression

Abstract

ABSTRACTAimMild 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.MethodsDepressive 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.ResultsMice 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.ConclusionPsychological 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.