Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic

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OBJECTIVE:To examine the effects of Yokukansan (YKS) extract on two endogenous modulators of anxiety,brain-derived neurotrophic factor (BDNF) and serotonin (5-HT)2A receptors pharmacologically,in the ischemic rat model of dementia.METHODS:The cerebral ischemia (CI) was induced by bilateral occlusion of the vertebral and common carotid arteries (4-vessel occlusion ischemia).The CI was combined with the amyloid-β42 peptide (Aβ 42) injected intracerebroventricularly,and referred to as CI+Aβ.Anxiety-like behaviors were assessed by elevated plus maze (enclosed arm),light/dark transition test (dark chamber),and open-field test.Wet-dog shakes were induced by the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI).The concentration of BDNF in serum was determined by enzyme-linked immuno sorbent assay.RESULTS:CI + Aβ increased anxiety,as demonstrated by the increase of time spent in the enclosed arms and dark chambers,and locomotion in the outer zone of the open field (thigmotaxis).CI + Aβ decreased the serum concentration of BDNF.YKS reduced the anxiety-like behaviors,suppressed the DOI-induced wet-dog shakes and increased serum BDNF concentrations.CONCLUSION:Our findings suggest that YKS extract improves CI + Aβ-induced anxiety by antagonizing 5-HT2A receptors and increasing BDNF.
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