Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic factor in rats with cerebral ischemia combined with amyloid-β42 peptide

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-HT_2A 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-HT_2A receptors and increasing BDNF.