Xiao-fei Chen, Zeng Jin, Ying-Zi Gong
Aug 1, 2018
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Influential Citations
21
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Quality indicators
Journal
Neuropharmacology
Abstract
ABSTRACT Most current antidepressants are lacking a pro‐cognition effect or even impair cognition as a side effect, and there are few effective psychopharmacological options that improve cognitive dysfunction in depression. Our previous studies revealed that hypidone hydrochloride (YL‐0919), a novel 5‐HT1A receptor partial agonist and SSRI, has antidepressant‐ and anxiolytic‐like effects. Here, further studies found that YL‐0919, but not vilazodone (a 5‐HT1A receptor partial agonist and SSRI), exerted a significant memory‐enhancing effect in the Morris water maze, object recognition test and step‐down passive avoidance task. Because the 5‐HT6 receptor has emerged as an interesting drug target to improve cognition, we investigated the target profile of YL‐0919 using radioligand binding assays, [35S]‐GTP&ggr;S binding and cAMP stimulation assays. YL‐0919 was found to act as a highly effective, full agonist of 5‐HT6 receptors. Finally, we observed that the memory‐enhancing activities of YL‐0919 were completely reversed after co‐administration of SB271046 (a selective 5‐HT6 receptor antagonist) at a dose that does not alter cognition. In summary, the findings of the current study suggest that YL‐0919 has clear memory‐enhancing effects, which might be at least partially mediated by 5‐HT6 receptor activation. HIGHLIGHTSYL‐0919 was found to act as a highly effective, full agonist of 5‐HT6 receptors.YL‐0919 has clear memory‐enhancing effects on behaviours.Direct activation of 5‐HT6 receptors partially mediates the memory‐enhancing actions of YL‐0919.