Studies on the animal model of post-stroke depression and application of antipsychotic aripiprazole

• Published in: Behavioural brain research 2015-07, Vol.287, p.294-303
• Main Authors: Kim, Yu Ri, Kim, Ha Neui, Pak, Malk Eun, Ahn, Sung Min, Hong, Ki Hwan, Shin, Hwa Kyoung, Choi, Byung Tae
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - administration & dosage; Aripiprazole; Aripiprazole - administration & dosage; Behavior, Animal - drug effects; Brain - drug effects; Brain - pathology; Depression - drug therapy; Depression - etiology; Depression - pathology; Disease Models, Animal; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Infarction, Middle Cerebral Artery - complications; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Neuroprotection; Post-stroke depression; Stress, Psychological - complications; Stroke - complications
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.03.062

•Chronic mild stress after stroke showed neuronal loss and declined neurogenesis.•Chronic mild stress after stroke produced neuronal loss at lesion and exofocal sites.•Neurodegeneration by chronic mild stress is involved in a process of depression.•Aripiprazole treatment is effective in ameliorating characteristics of depression. We investigated the question of whether an animal model of post-stroke depression in ischemic stroke can be developed by additional chronic mild stress (CMS) procedures. Behavioral and histopathological analysis was performed for examination of the depressive disorders in CMS, left middle cerebral artery occlusion (MCAO) and CMS after MCAO (MCAO+CMS) in mice. In all depressant screening tests involving open field, sucrose preference, forced swim and Morris water maze test, MCAO+CMS mice showed more significant depressive behaviors than MCAO mice. MCAO+CMS mice also showed distinct deficits in forced swim and Morris water maze test compared with CMS. In the histopathological analysis, prominent atrophic changes were seen in the striatum and midbrain of MCAO treated mice compared with CMS. MCAO+CMS mice showed a decrease of proliferative and differentiated neuronal cells in the striatum and hippocampus with dopaminergic neuronal injuries in the midbrain as compared with CMS and MCAO alone treated mice. Treatment of MCAO+CMS mice with aripiprazole resulted in reduction of all depressive behaviors examined, particularly in the Morris water maze test. Recovered dopaminergic neuronal injuries in the midbrain and enhanced neurogenesis in the hippocampus were also demonstrated. Our results suggest that CMS after ischemic stroke can lead to severe depressive-like behavior compared with CMS or MCAO alone treated mice via neurodegeneration in the primary lesion and secondary extrafocal sites and degradation of neurogenesis, and these behavioral and histopathological changes are reversed by treatment with aripiprazole. Thus adjunct therapy with an antipsychotic may exert its antidepressant effects via neuroprotection and neurogenesis in CMS-treated ischemic mice.