title: Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke.
abstract: The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. sprout_ing@pusan.ac.kr.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea. sprout_ing@pusan.ac.kr.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. Kim.Haneui@mayo.edu.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea. Kim.Haneui@mayo.edu.
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Korea. kwhong@pusan.ac.kr.
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Hong
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. julie@pusan.ac.kr.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea. julie@pusan.ac.kr.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. julie@pusan.ac.kr.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. choibt@pusan.ac.kr.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea. choibt@pusan.ac.kr.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea. choibt@pusan.ac.kr.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000068180:Aripiprazole / Q000494:pharmacology*; D001284:Atrophy; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D050882:CREB-Binding Protein / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077407:Cilostazol; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D004357:Drug Synergism; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy / Q000473:pathology / Q000523:psychology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D013777:Tetrazoles; D000068180:Aripiprazole; D050882:CREB-Binding Protein; D000077407:Cilostazol
keywords: aripiprazole; chronic mild stress; cilostazol; depression; stroke