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Int. J. Mol. Sci. 2017, 18(2), 355; doi:10.3390/ijms18020355

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

1
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea
2
Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea
3
Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Korea
4
Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea
*
Authors to whom correspondence should be addressed.
Academic Editors: Ge Zhang, Cesar Borlongan and Michele Fornaro
Received: 22 September 2016 / Revised: 29 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
View Full-Text   |   Download PDF [6422 KB, uploaded 8 February 2017]   |  

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. View Full-Text
Keywords: aripiprazole; cilostazol; depression; stroke; chronic mild stress aripiprazole; cilostazol; depression; stroke; chronic mild stress
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MDPI and ACS Style

Kim, Y.R.; Kim, H.N.; Hong, K.W.; Shin, H.K.; Choi, B.T. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke. Int. J. Mol. Sci. 2017, 18, 355.

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